Human Molecular Genetics, 2000, Vol. 9, No. 6 909-916
© 2000 Oxford University Press
Fourteen and counting: unraveling trinucleotide repeat diseases
1Program in Cell and Molecular Biology, Departments of Pediatrics, Molecular and Human Genetics, Baylor College of Medicine and 2Howard Hughes Medical Institute, Houston, TX 77030, USA
Received 4 February 2000; Accepted 8 February 2000.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONNON-CODING TRINUCLEOTIDE REPEAT...POLYGLUTAMINE DISEASESCONCLUSIONREFERENCES |
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The pathological expansion of unstable trinucleotide repeats currently is known to cause 14 neurological diseases. Over the past several years, researchers have concentrated on the challenging task of identifying the mechanism by which the expanded trinucleotide repeat leads to abnormal cellular function. As a consequence, the trinucleotide repeat field has grown dramatically since the initial discovery of dynamic mutations less than a decade ago. Trinucleotide repeat expansions may prove to cause pathology through a variety of mechanisms including interference with DNA structure, transcription, RNA–protein interaction and altered protein conformations/interactions. The goal of this review is to provide a brief description of the genes harboring expanded repeats, coupled with new insights into the molecular pathways most likely to be disrupted by these expansions. Data from studies of patient material, cell culture and animal models demonstrate the complexity of the pathogenic mechanisms in each of the diseases.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONNON-CODING TRINUCLEOTIDE REPEAT...POLYGLUTAMINE DISEASESCONCLUSIONREFERENCES |
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Trinucleotide repeats were once thought to be commonplace iterations in the genome, but the 1990s taught us differently. These apparently ‘benign’ stretches of DNA can sometimes expand and cause disease. Several defining features are shared amongst disorders caused by trinucleotide repeat expansions. First, the mutant repeats show both somatic and germline instability and, more frequently, they expand rather than contract in successive transmissions. Secondly, an earlier age of onset and increasing severity of phenotype in subsequent generations (anticipation) generally are correlated with larger repeat length. Finally, the parental origin of the disease allele can often influence anticipation, with paternal transmissions carrying a greater risk of expansion for many of these disorders.
Trinucleotide repeat diseases can be categorized into two subclasses based on the relative location of the trinucleotide repeat to a gene. The first subclass, presently accounting for six diseases, has its repeats in non-coding sequences (Table 1), whereas the second subclass is characterized by exonic (CAG)n repeats that code for polyglutamine tracts. The latter group is referred to collectively as ‘polyglutamine diseases’ (Table 2). This review summarizes the most recent developments in understanding the molecular mechanisms at work in these two subclasses of diseases.
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NON-CODING TRINUCLEOTIDE REPEAT DISORDERS |
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TOPABSTRACTINTRODUCTIONNON-CODING TRINUCLEOTIDE REPEAT...POLYGLUTAMINE DISEASESCONCLUSIONREFERENCES |
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The non-coding trinucleotide repeat diseases typically are characterized by large and variable repeat expansions that result in multiple tissue dysfunction or degeneration. Phenotypic manifestations within a disease are variable, perhaps owing to a pronounced degree of somatic heterogeneity. The larger mutations often are transmitted from a small pool of clinically silent intermediate size expansions, termed pre-mutations. Despite these similarities, the trinucleotide repeat sequences vary in this subclass (CGG, GCC, GAA, CTG and CAG), and it is clear that the particular trinucleotide sequence, as well as its location with respect to a gene, are important defining factors in dictating the unique mechanism of pathogenesis for each disease. The pathogenic mechanism will also vary from disease to disease, depending on the consequences of the lost function of the respective proteins or, in some cases, acquired function of a toxic transcript. As each of these diseases may have unique pathophysiologies they will be discussed individually in the following sections.
Fragile X syndrome (FRAXA)
Fragile X syndrome is characterized primarily by mental retardation, macroorchidism, some dysmorphic features and hyperactivity. The disease is caused by expansion of a polymorphic (CGG)n repeat in the 5'-untranslated region (UTR) of the fragile X mental retardation gene (FMR1) (1,2). Expansion of the CGG repeat beyond 230 trinucleotides results in its hypermethylation together with a CpG island within the FMR1 promoter region (3). This hypermethylation recruits transcriptional silencing machinery to the FMR1 gene, followed by reduced FMR1 transcription and loss of gene product (FMRP) (4–7). The mutation in fragile X syndrome is therefore a loss of the normal function of FMRP. With two K homology domains and an RGG box, FMRP is an RNA-binding protein that shuttles between the nucleus and the cytoplasm (3). In the cytoplasm, FMRP forms messenger ribonucleoprotein (mRNP) complexes and associates with ribosomes. FMR1 has highest expression in the brain. In neurons, FMRP’s association with the translational machinery in the dendritic spines suggests that it may play a role in modulating the localization and/or translation of specific target mRNAs. Therefore, mental retardation in FRAXA may result from improper protein translation during synaptic development or maintenance. The other phenotypes associated with fragile X syndrome may stem from the potential pleiotropic effects caused by abnormal RNA regulation. FMRP and two related proteins, FXR1P and FXR2P, show significant homology (60%) including conservation of the RNA-binding domains (8,9). These proteins are capable of interacting as homodimers and heterodimers and can be co-immunoprecipitated as a complex, suggesting a functional role as a ribonucleoprotein complex (10,11). Nucleolin and NUFIP (nuclear FMRP-interacting protein) are two other FMRP-associated proteins recently identified (12,13). The physiological significance of these new interactors is not yet known, but they may function as part of the FMRP–RNP complex that regulates specific RNA metabolism.
Fragile XE MR (FRAXE)
FRAXE patients have mild mental retardation and variable behavior abnormalities. FRAXE is caused by an expansion of a polymorphic (GCC)n repeat in the promoter region of the FMR2 gene (14,15). As with FRAXA, the expanded repeats are hypermethylated, leading to transcriptional silencing of FMR2 and subsequent loss of gene product (FMR2). Two other proteins, AF4 and LAF-4, share motifs with FMR2, and all three proteins exhibit nuclear localization, DNA-binding capacity and transcription transactivation potential (15). The putative role of FMR2 as a transcriptional activator together with its high expression levels in the hippocampus and the amygdala suggest that the cognitive and behavioral deficits in FRAXE are due to alterations in neuronal gene regulation (16–18).
Friedreich ataxia (FRDA)
Friedreich ataxia is autosomal recessive and is therefore the only triplet repeat disorder that does not show anticipation. FRDA is characterized by ataxia, dysarthria, diminished reflexes, cardiomyopathy and diabetes. Degeneration is evident in the spinal cord, dorsal root ganglia and several peripheral sensory systems. FRDA is caused by a large intronic GAA repeat expansion in the X25 gene (or frataxin) which leads to reduced X25 expression (19,20). The expanded AT-rich sequence most probably causes transcriptional interference via a self-association of the GAA/TTC tract, which stabilizes the DNA in a triplex structure (21). Reduced X25 mRNA decreases frataxin levels, suggesting that FRDA results from a partial loss of frataxin function (20,22–25). Disruption of the yeast X25 homolog (YFH1) causes abnormal accumulation of mitochondrial iron, loss of mtDNA, respiratory dysfunction, multiple iron–sulfur-dependent enzyme deficiencies and increased sensitivity to oxidative stress (22,26–29). These findings, together with highly conserved mitochondrial targeting signal sequences and mitochondrial membrane localization in yeast and human, suggest that frataxin is involved in iron homeostasis and respiratory function (22,26–29). In FRDA samples, studies have shown increased iron content, deficient activities of proteins involved in iron–sulfur homeostasis and hypersensitivity to iron and H2O2 stress (30–32). Therefore, frataxin insufficiency may result in abnormal iron–sulfur homeostasis and, in turn, mitochondrial dysfunction, free radical production, oxidative stress and cellular degeneration.
Myotonic dystrophy (DM)
DM is a multisystem disorder with highly variable phenotypes and anticipation. Myotonia, muscle weakness and progressive muscle wasting characterize adult-onset DM. Developmental abnormalities, mental handicap, hypotonia and respiratory distress are often evident in the more severe congenital myotonic dystrophy (CDM). DM is caused by an expanded CTG trinucleotide repeat tract in the 3'-UTR of the protein kinase gene, DMPK (33–36). The pathophysiology of DM is complex and may involve a combination of molecular defects that have varying consequences for different tissues during development. The CTG repeat may alter DMPK levels indirectly by interfering with DMPK transcription, RNA processing and/or translation. The result would be abnormal phosphorylation of downstream substrates. Studies from a mouse model lacking DMPK, however, argue that loss of DMPK function is not sufficient to cause the phenotypic spectrum of DM (37,38). The identification of two other genes flanking DMPK raised the possibility that CTG expansion may have cis-chromatin effects that could alter neighboring gene expression (39). The CTG repeat is located within the promoter of a downstream homeobox gene, termed DM locus-associated homeodomain protein (DMAHP), and immediately upstream of DMPK is gene 59 (also known as DMWD). Loss of function of either or both of these proteins could contribute to some of the features in DM. Another proposed mechanism of pathogenesis is based on a gain of function or trans-dominant effect of the CTG-expanded transcript, which could interfere with the normal processing and/or metabolism of various RNAs. Altered metabolism of tissue-specific RNAs could account for the various symptoms seen in DM patients. The expanded CUG repeat may sequester RNA-binding proteins, such as the CUG-binding protein (CUG-BP or hNab50), thereby interfering with their normal role in regulating RNA processing (40–45).
Spinocerebellar ataxia type 8 (SCA8)
SCA8 is a progressive ataxia with cerebellar atrophy, decreased vibration sense and brisk reflexes. Correlating with the phenotype, SCA8 is expressed primarily in the brain, and disease is caused by an expanded CTG repeat in its 3'-terminal exon (46–48). Interestingly, SCA8 may have a CTG repeat range that is pathogenic (~110–250 repeats), with shorter and larger repeats not resulting in disease (49). Also uniquely amongst triplet repeat disorders, the SCA8 transcript does not code for a protein and may be an endogenous antisense RNA that regulates the expression of another gene(s). A second mRNA, transcribed in an orientation opposite to that of the SCA8 transcript, contains a common region of overlap. This ‘sense’ transcript encodes a protein that shares homology with the Drosophila KELCH gene (KLHL1) (50). Although the normal function of KLHL1 in the brain is not understood, it has a conserved Kelch actin-binding domain and POZ/BTB protein–protein domains.
Spinocerebellar ataxia type 12 (SCA12)
SCA12 is a rare disease caused by a non-coding CAG trinucleotide repeat expansion in the 5'-UTR of the PPP2R2B gene (or PP2A-PR55ß) (51). PPP2R2B encodes a brain-specific regulatory subunit of protein phosphatase 2A (PP2A). Although the CAG repeat is located near conserved promoter elements and transcriptional start sites, repeat-mediated transcriptional interference of PPP2R2B has not yet been shown. Future expression and function analysis of PP2A-PR55ß will provide essential clues toward understanding the pathophysiology of SCA12.
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POLYGLUTAMINE DISEASES |
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TOPABSTRACTINTRODUCTIONNON-CODING TRINUCLEOTIDE REPEAT...POLYGLUTAMINE DISEASESCONCLUSIONREFERENCES |
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In comparison with the non-coding disorders, polyglutamine diseases have repeat expansions that are much smaller in size and variation. Although the mutant proteins do not share any homology outside the polyglutamine tract, the polyglutamine diseases have several similar features and probably share common mechanisms of pathogenesis. All eight known polyglutamine disorders are characterized by progressive neuronal dysfunction that typically begins in mid-life and results in severe neurodegeneration. Despite the ubiquitous expression of all eight genes, only a certain subset of neurons is vulnerable to degeneration. Studies of animal models and tissue culture systems have clearly demonstrated that these diseases are caused by a gain-of-function mechanism and that the expanded polyglutamine tracts are at the core of pathogenesis (52,53). Although expanded glutamine tracts in isolation are extremely toxic to cells, the selective neuronal loss particular to each disease occurs only when the full-length protein harboring an expanded glutamine tract is expressed. This idea is well supported by several recent studies of mice that were engineered to express either full-length HD or DRPLA with an expanded number of CAG repeats, and indicates that protein context helps to mediate the selective neuronal vulnerability (54–59).
Two early models were proposed to explain how long polyglutamine tracts might be toxic to neurons. Green (60) proposed that the extended polyglutamine tract is a transglutaminase substrate that can become cross-linked via isopeptide bonds. This event may enhance polyglutamine-mediated aggregation and toxicity in affected neurons (61–63). Perutz et al. (64) suggested that the expanded polyglutamine repeats organize into polar zippers and then aggregate. The idea that the glutamine expansion destabilizes the native conformations of the mutant proteins is extended by numerous studies of cell culture systems, animal models and patient tissues that show mutant polyglutamine protein aggregates (52,53,65). Ubiquitin-positive protein aggregates, primarily found in the nucleus, have now been reported for seven of these diseases, the exception being SCA6 where aggregates are cytoplasmic and ubiquitin negative (53,66,67). Additionally, protein aggregates with similar structure to nuclear inclusions (NIs) have been reported in the neuropil of Huntington’s disease (HD) brains and transgenic mice (68,69). Occurring in dendrites and dendritic spines, neuropil aggregates are far more common in HD brains than NIs, and their appearance is well correlated with neurological findings in patients and HD mice (68,69).
Initially, the discovery of the NI was exciting as it suggested a common pathogenic mechanism for all polyglutamine disorders; namely, aggregates cause aberrant protein–protein interactions that affect either nuclear architecture and function and/or the function of interacting proteins. Recent findings, however, strongly indicate that NIs are neither necessary nor sufficient to initiate polyglutamine-mediated disease. First, the regional distribution of the NIs in tissue from spinal and bulbar muscular atrophy (SBMA), HD, SCA2 and SCA7 patients does not always correspond to the selective pathology (67,68,70–74). In animal models for HD, NIs were either: (i) detected in large quantities in cells that show no signs of degeneration; or (ii) detected with a very low frequency (<1%) in the striatum where the neuronal loss was prominent (54,55,75,76). Moreover, SCA1 transgenic mice expressing mutant ataxin-1 lacking the self-association region—which is essential for ataxin-1 dimerization—develop ataxia and Purkinje cell pathology but without apparent ataxin-1 aggregation (77).
Protein misfolding and the ubiquitin–proteasome pathway
Despite evidence that indicates that NIs are dissociated from polyglutamine-induced toxicity, it is striking that expanded protein aggregates are found in all polyglutamine diseases. Even though the NIs are not the initial cause of disease, unraveling the process by which they originate may provide insight into the pathogenesis of polyglutamine disorders. A model would be that the expansion of the glutamine tract results in a misfolded protein that gains a toxic function. Expanded polyglutamine proteins may adopt energetically stable structures, which resist unfolding and therefore impede clearance by the proteasome. For example, polyglutamine-expanded ataxin-1 (92Q) is considerably more resistant to ubiquitin-mediated degradation in vitro compared with wild-type ataxin-1 (2Q) (78). Misfolded and potentially with extended half-lives, these proteins may interact with other proteins in an aberrant fashion and thereby trigger selective degeneration. If the capacity of the intracellular system handling these proteins is exceeded, then the NIs may develop and a cellular response to the extended presence of the mutant protein may eventuate. This concept is supported by the observation that proteasome inhibition promotes aggregation of mutant ataxin-1 and ataxin-3 in cell culture (78,79) and, in patient tissue, animal models and tissue culture systems, the proteasome and several molecular chaperones redistribute to the sites of protein aggregation (79–84). By overexpressing a dominant-negative ubiquitin-conjugating enzyme (UBC) and presumably altering the ubiquitination and clearance of mutant huntingtin in cell culture, Saudou et al. (85) were able to inhibit NI formation while accelerating cell death. Similarly, when crossing the SCA1 transgenic mice with mice that lack Ube3A, an E3 ubiquitin–protein ligase, we discovered that Purkinje cells from the SCA1/Ube3a mice had significantly fewer NIs than SCA1 littermates but markedly worse SCA1 pathology (Fig. 1A–D) (78). Together, these data suggest that impaired proteasomal degradation of mutant polyglutamine proteins may contribute to pathogenesis but, more importantly, the mutant proteins may be more toxic if not properly ubiquitinated, turned-over or possibly sequestered to an NI.
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That molecular chaperones redistribute to NIs suggests that a chaperone stress response is being mounted to cope potentially with the toxic presence of misfolded polyglutamine proteins. Since molecular chaperones are known to be instrumental in proper protein folding, ubiquitin-dependent degradation and suppression of protein aggregation, we might infer that the cellular levels of a chaperone could directly mediate the aggregation and/or turnover of a mutant polyglutamine protein. Support for this inference comes from the fact that molecular chaperones, when overexpressed in cell culture, can decrease both the size and frequency of nuclear aggregates (80,81,84) and this decrease can be correlated with a decrease in toxicity (81). Will the chaperone-mediated benefits seen in cell culture occur, without any adverse effects, in patients? Recent data from studies of Drosophila models of polyglutamine disease are encouraging (86,87). In two independent studies, neurons expressing peptides with expanded glutamine repeats degenerated and showed numerous nuclear aggregates. Warrick et al. (88) further showed that a dominant-negative form of a fly Hsp70 enhances degeneration in the flies expressing an MJD peptide (78Q). More exciting was the observation that overexpression of Hsp70 suppresses polyglutamine-induced neurodegeneration in this animal model (Fig. 1E–H). Importantly, this suppression occurred without any effect on NI formation, arguing further against a correlation between polyglutamine-induced toxicity and NI formation.
Nuclear localization and gene expression
For most of the polyglutamine diseases, the protein aggregates are found predominantly in the nucleus, which is interesting given the varying subcellular localization of the soluble forms of these proteins. Is nuclear localization of the mutant proteins a critical event in polyglutamine disease and if so how do the mutant proteins affect nuclear function? The importance of nuclear localization of mutant ataxin-1 is evident from studies of SCA1 transgenic mice that overexpress expanded ataxin-1 (82Q) with a mutated nuclear localization signal (NLS) (77). These mice had abundant levels of cytoplasmic mutant ataxin-1, but they never developed ataxia or pathology. Similarly, in cell culture models of HD, the addition of a nuclear export signal to mutant huntingtin drives it to the cytoplasm, and thereby suppresses aggregation and cell death; the opposite effect is seen with the addition of an NLS (85,89).
Once inside the nucleus, several recent reports suggest that mutant polyglutamine proteins may affect gene expression. For example, N-terminal huntingtin interacts in a repeat-dependent manner with the nuclear receptor co-repressor (N-CoR), which is known to repress transcription from ligand-activated receptors (90). Subcellular localization studies demonstrated that N-CoR and other associated co-repressors are redistributed by mutant huntingtin, suggesting that altered transcriptional regulation may be involved in HD. In cell culture, overexpression of full-length ataxin-1 and ataxin-7 causes these proteins to localize to the nucleus and form nuclear matrix-associated aggregates that may affect the promyelocytic oncogenic domains (PODs; also thought to be important in transcriptional regulation) (91,92). Full-length mutant AR accumulates in both cytoplasmic and nuclear matrix-associated aggregates when overexpressed in tissue culture cells, and these aggregates caused redistribution of the steroid receptor coactivator (SRC1), suggesting that SRC1-mediated transcription pathways might be affected in SBMA (84). NIs are known to sequester other polyglutamine-containing proteins, such as the TATA-binding protein (TBP) (93). Interestingly, expansion of the CAG repeat in the TBP gene may also be responsible for neurodegenerative disease (94). Analogously to the gain-of-function mechanisms in DM, but at the protein level, mutant polyglutamine repeat proteins may sequester poly(Q)-binding proteins important in transcriptional regulation. Waragai et al. (95) demonstrated that a polyglutamine tract-binding domain protein (PQBP-1) interacts with the glutamine tract in transcription factors and polyglutamine repeat disease proteins. This interaction is strengthened in a length-dependent manner and may affect cell survival in vitro. Also in vivo, several neuronal genes involved in calcium homeostasis and signal transduction are down-regulated specifically by the expression of expanded ataxin-1 in SCA1 transgenic mice. It is noteworthy that these alterations required nuclear localization of mutant ataxin-1 and occurred prior to any detectable pathology or visible NIs (96). Together, these results suggest that regulation of gene expression may be an important and early molecular player in the pathogenesis of polyglutamine disease.
Cleavage, caspase activity and apoptosis
Numerous studies indicate that many of the polyglutamine proteins must first be proteolytically cleaved in order to translocate to the nucleus and exert their toxic effect (53). The search for proteases that mediate this processing event has revealed that huntingtin, AR, atrophin-1 and ataxin-3 are all substrates for one or more caspases (cysteine proteases involved in apoptosis) (97,98). Sanchez et al. (99) proposed that aggregates of polyglutamine repeat proteins can sequester one or more procaspases, which become activated and set off the apoptotic pathway. These authors found activated caspase-8 uniquely in affected HD brain extracts, but not in controls. Additionally, preventing caspase-8-mediated apoptosis hin- dered the polyglutamine-induced cell death in cell culture. Caspase-1 is also activated in HD brains and transgenic mice (100). When Ona et al. (100) inhibited its activity in HD mice, endogenous huntingtin cleavage was reduced and the progression of several of the pathological features in this animal model was slowed. These results raise the possibility that caspase activity has a role in polyglutamine disease; however, the steps involved in this pathway are not yet clear. Is one or more caspase activity responsible for liberating the toxic polyglutamine peptides? Does the apoptotic pathway play a primary role in neuronal dysfunction, or is it a secondary event that occurs in dysfunctional neurons that can no longer tolerate the toxic effects of the mutant protein? Future studies will need to address the underlying pathogenic mechanisms involved in caspase activation and reconcile their relationship to the selective pattern of degeneration seen in each disorder.
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CONCLUSION |
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TOPABSTRACTINTRODUCTIONNON-CODING TRINUCLEOTIDE REPEAT...POLYGLUTAMINE DISEASESCONCLUSIONREFERENCES |
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The discovery of each new triplet repeat disorder brings tremendous clinical benefits, offering better classification of the diseases and facilitating early diagnosis and genetic counseling. Studies to date have made it clear that the pathological mechanisms in trinucleotide repeat disorders are complex, probably involving more than one mechanism of pathogenesis. The importance of animal models in dissecting each of these mechanisms is becoming increasingly apparent especially with the emerging insights gained from the application of fly and yeast genetics and from genetically engineered mice. Future clinical benefits will also come from advances in gene chip technologies and the human genome initiative, which together could accelerate the pace of identifying new therapeutic strategies to modulate the iron abnormalities in FRDA, or the putative alterations in gene/RNA regulation in FRAXA, FRAXE, DM and the polyglutamine disorders. Understanding the mutations in polyglutamine diseases in terms of their effect on protein–protein interactions and turnover, together with studies aimed at enhancing proper folding and degradation, may be invaluable tools required to slow or prevent these diseases. In fact, it may be possible to adopt these tools to identify therapies for other neurodegenerative ‘proteinopathies’ such as Alzheimer’s disease, amyotrophic lateral sclerosis, prion diseases and Parkinson’s disease. Despite the enormous amount of headway made in just the last few years, a sea of questions remains to be explored. Perhaps the most puzzling is a teleological one—why have these repeats expanded in the first place and what biological role do they have in evolution?
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FOOTNOTES |
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+ To whom correspondence should be addressed at: Baylor College of Medicine, Howard Hughes Medical Institute, One Baylor Plaza, Room T807, Houston, TX 77030-3498, USA. Tel: +1 713 798 6558; Fax: +1 713 798 8728; Email: hzoghbi@bcm.tmc.edu
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REFERENCES |
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1 Fu, Y.-H., Kuhl, D.P.A., Pizutti, A., Pieretti, M., Sutcliffe, J.S., Richards, S., Verkerk, A.J.M.H., Holden, J.J.A., Fenwick Jr, R.G., Warren, S.T. et al. (1991) Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell, 67, 1047–1058.[Web of Science][Medline]
2 Verkerk, A.J.M.H., Pieretti, M., Sutcliffe, J.S., Fu, Y.-H., Kuhl, D.P.A., Pizutti, A., Reiner, O., Richards, S., Victoria, M.F., Zhang, R. et al. (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 65, 905–914.[Web of Science][Medline]
3 Eichler, E.E. and Nelson, D.L. (1998) The FRAXA fragile site and fragile X syndrome. In Rubinsztein, D.C. and Hayden, M.R. (eds), Analysis of Triplet Repeat Disorders. BIOS Scientific, Oxford, UK, pp. 13–39.
4 Eberhart, D.E. and Warren, S.T. (1996) Nuclease sensitivity of permeabilized cells confirms altered chromatin formation at the fragile X locus. Somat. Cell Mol. Genet., 22, 435–441.[Web of Science][Medline]
5 Drouin, R., Angers, M., Dallaire, N., Rose, T.M., Khandjian, W. and Rousseau, F. (1997) Structural and functional characterization of the human FMR1 promoter reveals similarities with the hnRNP-A2 promoter region. Hum. Mol. Genet., 6, 2051–2060.
6 Schwemmle, S., de Graaff, E., Deissler, H., Glaser, D., Wohrle, D., Kennerknecht, I., Just, W., Oostra, B.A., Dorfler, W., Vogel, W. et al. (1997) Characterization of FMR1 promoter elements by in vivo-footprinting analysis. Am. J. Hum. Genet., 60, 1354–1362.[Web of Science][Medline]
7 Coffee, B., Zhang, F., Warren, S.T. and Reines, D. (1999) Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells. Nature Genet., 22, 98–101.[Web of Science][Medline]
8 Siomi, M.C., Siomi, H., Sauer, W.H., Srinivasan, S., Nussbaum, R.L. and Dreyfuss, G. (1995) FXR1, an autosomal homolog of the fragile X mental retardation gene. EMBO J., 14, 2401–2408.[Web of Science][Medline]
9 Kirkpatrick, L.L., McIlwain, K.A. and Nelson, D.L. (1999) Alternative splicing in the murine and human FXR1 genes. Genomics, 59, 193–202.[Web of Science][Medline]
10 Zhang, Y., O’Connor, J.P., Siomi, M.C., Srinivasan, S., Dutra, A., Nussbaum, R.L. and Dreyfuss, G. (1995) The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J., 14, 5358–5366.[Web of Science][Medline]
11 Tamanini, F., Willemsen, R., van Unen, L., Bontekoe, C., Galjaard, H., Oostra, B.A. and Hoogeveen, A.T. (1997) Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis. Hum. Mol. Genet., 6, 1315–1322.
12 Bardoni, B., Schenck, A. and Mandel, J.L. (1999) A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein. Hum. Mol. Genet., 8, 2557–2566.
13 Ceman, S., Brown, V. and Warren, S.T. (1999) Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex. Mol. Cell. Biol., 19, 7925–7932.
14 Knight, S.J., Flannery, A.V., Hirst, M.C., Campbell, L., Christodoulou, Z., Phelps, S.R., Pointon, J., Middleton-Price, H.R., Barnicoat, A., Pembrey, M.E. et al. (1993) Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell, 74, 127–134.[Web of Science][Medline]
15 Skinner, J.A., Foss, G.S., Miller, W.J. and Davies, K.E. (1998) Molecular studies of the fragile FRAXE and FRAXF. In Rubinsztein, D.C. and Hayden, M.R. (eds), Analysis of Triplet Repeat Disorders. BIOS Scientific, Oxford, UK, pp. 51–58.
16 Chakrabarti, L., Knight, S.J., Flannery, A.V. and Davies, K.E. (1996) A candidate gene for mild mental handicap at the FRAXE fragile site. Hum. Mol. Genet., 5, 275–282.
17 Gecz, J., Oostra, B.A., Hockey, A., Carbonell, P., Turner, G., Haan, E.A., Sutherland, G.R. and Mulley, J.C. (1997) FMR2 expression in families with FRAXE mental retardation. Hum. Mol. Genet., 6, 435–441.
18 Chakrabarti, L., Bristulf, J., Foss, G.S. and Davies, K.E. (1998) Expression of the murine homologue of FMR2 in mouse brain and during development. Hum. Mol. Genet., 7, 441–448.
19 Campuzano, V., Montermini, L., Molto, M.D., Pianese, L., Cossee, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A. et al. (1996) Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science, 271, 1423–1427.[Abstract]
20 Cossee, M., Campuzano, V., Koutnikova, H., Fischbeck, K., Mandel, J.L., Koenig, M., Bidichandani, S.I., Patel, P.I., Molte, M.D., Canizares, J. et al. (1997) Frataxin fracas. Nature Genet., 15, 337–338.[Web of Science][Medline]
21 Sakamoto, N., Chastain, P.D., Parniewski, P., Ohshima, K., Pandolfo, M., Griffith, J.D. and Wells, R.D. (1999) Sticky DNA: self-association properties of long GAA·TTC repeats in R·R·Y triplex structures from Friedreich’s ataxia. Mol. Cell, 3, 465–475.[Web of Science][Medline]
22 Campuzano, V., Montermini, L., Lutz, Y., Cova, L., Hindelang, C., Jiralerspong, S., Trottier, Y., Kish, S.J., Faucheux, B., Trouillas, P. et al. (1997) Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum. Mol. Genet., 6, 1771–1780.
23 Bartolo, C., Mendell, J.R. and Prior, T.W. (1998) Identification of a missense mutation in a Friedreich’s ataxia patient: implications for diagnosis and carrier studies. Am. J. Med. Genet., 79, 396–399.[Web of Science][Medline]
24 Bidichandani, S., Ashizawa, T. and Patel, P.I. (1998) The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. Am. J. Hum. Genet., 62, 111–121.[Web of Science][Medline]
25 Ohshima, K., Montermini, L., Wells, R.D. and Pandolfo, M. (1998) Inhibitory effects of expanded GAA·TTC triplet repeats from intron I of the Friedreich ataxia gene on transcription and replication in vivo. J. Biol. Chem., 273, 14588–14595.
26 Babcock, M., de Silva, D., Oaks, R., Davis-Kaplan, S., Jiralerspong, S., Montermini, L., Pandolfo, M. and Kaplan, J. (1997) Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science, 276, 1709–1712.
27 Foury, F. and Cazzalini, O. (1997) Deletion of the yeast homologue of the human gene associated with Friedreich’s ataxia elicits iron accumulation in mitochondria. FEBS Lett., 411, 373–377.[Web of Science][Medline]
28 Koutnikova, H., Campuzano, V., Foury, F., Dolle, P., Cazzalini, O. and Koenig, M. (1997) Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin. Nature Genet., 16, 345–351.[Web of Science][Medline]
29 Wilson, R.B. and Roof, D.M. (1997) Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue. Nature Genet., 16, 352–357.[Web of Science][Medline]
30 Lamarche, J.B., Cote, M. and Lemieux, B. (1980) The cardiomyopathy of Friedreich’s ataxia morphological observations in 3 cases. Can. J. Neurol. Sci., 7, 389–396.[Web of Science][Medline]
31 Rotig, A., de Lonlay, P., Chretien, D., Foury, F., Koenig, M., Sidi, D., Munnich, A. and Rustin, P. (1997) Aconitase and mitochondrial iron–sulphur protein deficiency in Friedreich ataxia. Nature Genet., 17, 215.[Web of Science][Medline]
32 Wong, A., Yang, J., Cavadini, P., Gellera, C., Lonnerdal, B., Taroni, F. and Cortopassi, G. (1999) The Friedreich’s ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis. Hum. Mol. Genet., 8, 425–430.
33 Brook, J.D., McCurrach, M.E., Harley, H.G., Buckler, A.J., Church, D., Aburatani, H., Hunter, K., Stanton, V.P., Thirion, J.P., Hudson, T. et al. (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell, 68, 799–808.[Web of Science][Medline]
34 Buxton, J., Shelbourne, P., Davies, J., Jones, C., Van Tongeren, T., Aslanidis, C., de Jong, P., Jansen, G., Anvret, M., Riley, B. et al. (1992) Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature, 355, 547–548.[Medline]
35 Fu, Y.-H., Pizutti, A., Fenwick, R.G., King, J.J., Rajnarayan, S., Dunne, P.W., Dubel, J., Nasser, G.A., Ashizawa, T., De Jong, P. et al. (1992) An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science, 255, 1256–1259.
36 Mahadevan, M., Tsilfidis, C., Sabourin, L., Shutler, G., Amemiya, C., Jansen, G., Neville, C., Narang, M., Barcelo, J., O’Hoy, K. et al. (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science, 255, 1253–1255.
37 Jansen, G., Groenen, P.J., Bachner, D., Jap, P.H., Coerwinkel, M., Oerlemans, F., van den Broek, W., Gohlsch, B., Pette, D., Plomp, J.J. et al. (1996) Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice. Nature Genet., 13, 316–324.[Web of Science][Medline]
38 Reddy, S., Smith, D.B., Rich, M.M., Leferovich, J.M., Reilly, P., Davis, B.M., Tran, K., Rayburn, H., Bronson, R., Cros, D. et al. (1996) Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy. Nature Genet., 13, 325–335.[Web of Science][Medline]
39 Korade-Mirnics, Z., Babitzke, P. and Hoffman, E. (1998) Myotonic dystrophy: molecular windows on a complex etiology. Nucleic Acids Res., 26, 1363–1368.
40 Timchenko, L.T., Miller, J.W., Timchenko, N.A., DeVore, D.R., Datar, K.V., Lin, L., Roberts, R., Caskey, C.T. and Swanson, M.S. (1996) Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res., 24, 4407–4414.
41 Timchenko, L.T., Timchenko, N.A., Caskey, C.T. and Roberts, R. (1996) Novel proteins with binding specificity for DNA CTG repeats and RNA CUG repeats: implications for myotonic dystrophy. Hum. Mol. Genet., 5, 115–121.
42 Roberts, R., Timchenko, N.A., Miller, J.W., Reddy, S., Caskey, C.T., Swanson, M.S. and Timchenko, L.T. (1997) Altered phosphorylation and intracellular distribution of a (CUG)n triplet repeat RNA-binding protein in patients with myotonic dystrophy and in myotonin protein kinase knockout mice. Proc. Natl Acad. Sci. USA, 94, 13221–13226.
43 Philips, A.V., Timchenko, L.T. and Cooper, T.A. (1998) Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy. Science, 280, 737–741.
44 Amack, J.D., Paguio, A.P. and Mahadevan, M.S. (1999) Cis and trans effects of the myotonic dystrophy (DM) mutation in a cell culture model. Hum. Mol. Genet., 8, 1975–1984.
45 Lu, X., Timchenko, N.A. and Timchenko, L.T. (1999) Cardiac elav-type RNA-binding protein (ETR-3) binds to RNA CUG repeats expanded in myotonic dystrophy. Hum. Mol. Genet., 8, 53–60.
46 Schalling, M., Hudson, T.J., Buetow, K.H. and Housman, D.E. (1993) Direct detection of novel expanded trinucleotide repeats in the human genome. Nature Genet., 4, 135–139.[Web of Science][Medline]
47 Janzen, M.L., Moseley, M.L., Benzow, K.A., Day, J.W., Koob, M.D. and Ranum, L.P.W. (1999) Limited expression of SCA8 is consistent with cerebellar pathogenesis and toxic gain of function RNA model. Am. J. Hum. Genet. 65 (suppl.), A276.
48 Koob, M.D., Moseley, M.L., Schut, L.J., Benzow, K.A., Bird, T.D., Day, J.W. and Ranum, L.P. (1999) An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nature Genet., 21, 379–384.[Web of Science][Medline]
49 Ranum, L.P.W., Moseley, M.L., Leppert, M.F., van den Engh, G., La Spada, A.R., Koob, M.D. and Day, J.W. (1999) Massive CTG expansions and deletions may reduce penetrance of spinocerebellar ataxia type 8. Am. J. Hum. Genet., 65(suppl.), A466.
50 Koob, M.D., Moseley, M.L., Benzow, K.A., Johnson, C.M., Nemes, J.P., Ranum, L.P.W. and Day, J.W. (1999) The SCA8 transcript is an antisense RNA to a brain-specific transcript encoding a novel actin-binding protein (KLHL1). Am. J. Hum. Genet., 65(suppl.), A30.
51 Holmes, S.E., O’Hearn, E.E., McInnis, M.G., Gorelick-Feldman, D.A., Kleiderlein, J.J., Callahan, C., Kwak, N.G., Ingersoll-Ashworth, R.G., Sherr, M., Sumner, A.J. et al. (1999) Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12. Nature Genet., 23, 391–392.[Web of Science][Medline]
52 Lin, X., Cummings, C.J. and Zoghbi, H.Y. (1999) Expanding our understanding of polyglutamine diseases through mouse models. Neuron, 24, 499–502.[Web of Science][Medline]
53 Zoghbi, H.Y. and Orr, H.T. (1999) Polyglutamine diseases: protein cleavage and aggregation. Curr. Opin. Neurobiol., 9, 566–570.[Web of Science][Medline]
54 Reddy, P.H., Williams, M., Charles, V., Garrett, L., Pike-Buchanan, L., Whetsell Jr, W.O., Miller, G. and Tagle, D.A. (1998) Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nature Genet., 20, 198–202.[Web of Science][Medline]
55 Hodgson, J.G., Agopyan, N., Gutekunst, C.A., Leavitt, B.R., LePiane, F., Singaraja, R., Smith, D.J., Bissada, N., McCutcheon, K., Nasir, J. et al. (1999) A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron, 23, 181–192.[Web of Science][Medline]
56 Sato, T., Oyake, M., Nakamura, K., Nakao, K., Fukusima, Y., Onodera, O., Igarashi, S., Takano, H., Kikugawa, K., Ishida, Y. et al. (1999) Transgenic mice harboring a full-length human mutant DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients. Hum. Mol. Genet., 8, 99–106.
57 Sato, T., Yamada, M., Oyake, M., Nakao, K., Nakamura, K., Katsuki, M., Takahashi, H. and Tsuji, S. (1999) Transgenic mice harboring a full-length human DRPLA gene with highly expanded CAG repeats exhibit severe disease phenotype. Am. J. Hum. Genet., 65(suppl.), A30.
58 Shelbourne, P.F., Killeen, N., Hevner, R.F., Johnston, H.M., Tecott, L., Lewandoski, M., Ennis, M., Ramirez, L., Li, Z., Iannicola, C. et al. (1999) A Huntington’s disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice. Hum. Mol. Genet., 8, 763–774.
59 Usdin, M.T., Shelbourne, P.F., Myers, R.M. and Madison, D.V. (1999) Impaired synaptic plasticity in mice carrying the Huntington’s disease mutation. Hum. Mol. Genet., 8, 839–846.
60 Green, H. (1993) Human genetic diseases due to codon reiteration: relationship to an evolutionary mechanism. Cell, 74, 955–956.[Web of Science][Medline]
61 Igarashi, S., Koide, R., Shimohata, T., Yamada, M., Hayashi, Y., Takano, H., Date, H., Oyake, M., Sato, T., Sato, A. et al. (1998) Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch. Nature Genet., 18, 111–117.[Web of Science][Medline]
62 Karpuj, M.V., Garren, H., Slunt, H., Price, D.L., Gusella, J., Becher, M.W. and Steinman, L. (1999) Transglutaminase aggregates huntingtin into nonamyloidogenic polymers, and its enzymatic activity increases in Huntington’s disease brain nuclei. Proc. Natl Acad. Sci. USA, 96, 7388–7393.
63 Lesort, M., Chun, W., Johnson, G.V. and Ferrante, R.J. (1999) Tissue transglutaminase is increased in Huntington’s disease brain. J. Neurochem., 73, 2018–2027.[Web of Science][Medline]
64 Perutz, M.F., Johnson, T., Suzuki, M. and Finch, J.T. (1994) Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc. Natl Acad. Sci. USA, 91, 5355–5358.
65 Paulson, H.L. (1999) Protein fate in neurodegenerative proteinopathies: polyglutamine diseases join the (mis)fold. Am. J. Hum. Genet., 64, 339–345.[Web of Science][Medline]
66 Ishikawa, K., Fujigasaki, H., Saegusa, H., Ohwada, K., Fujita, T., Iwamoto, H., Komatsuzaki, Y., Toru, S., Toriyama, H., Watanabe, M. et al. (1999) Abundant expression and cytoplasmic aggregations of a1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6. Hum. Mol. Genet., 8, 1185–1193.
67 Koyano, S., Uchihara, T., Fujigasaki, H., Nakamura, A., Yagishita, S. and Iwabuchi, K. (1999) Neuronal intranuclear inclusions in spinocerebellar ataxia type 2: triple-labeling immunofluorescent study. Neurosci. Lett., 273, 117–120.[Web of Science][Medline]
68 Gutekunst, C.A., Li, S.H., Yi, H., Mulroy, J.S., Kuemmerle, S., Jones, R., Rye, D., Ferrante, R.J., Hersch, S.M. and Li, X.J. (1999) Nuclear and neuropil aggregates in Huntington’s disease: relationship to neuropathology. J. Neurosci., 19, 2522–2534.
69 Li, H., Li, S.H., Cheng, A.L., Mangiarini, L., Bates, G.P. and Li, X.J. (1999) Ultrastructural localization and progressive formation of neuropil aggregates in Huntington’s disease transgenic mice. Hum. Mol. Genet., 8, 1227–1236.
70 Holmberg, M., Duyckaerts, C., Durr, A., Cancel, G., Gourfinkel-An, I., Damier, P., Faucheux, B., Trottier, Y., Hirsch, E.C., Agid, Y. et al. (1998) Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions. Hum. Mol. Genet., 7, 913–918.
71 Li, M., Miwa, S., Kobayashi, Y., Merry, D.E., Yamamoto, M., Tanaka, F., Doyu, M., Hashizume, Y., Fischbeck, K.H. and Sobue, G. (1998) Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann. Neurol., 44, 249–254.[Web of Science][Medline]
72 Li, M., Nakagomi, Y., Kobayashi, Y., Merry, D.E., Tanaka, F., Doyu, M., Mitsuma, T., Hashizume, Y., Fischbeck, K.H. and Sobue, G. (1998) Nonneural nuclear inclusions of androgen receptor protein in spinal and bulbar muscular atrophy. Am. J. Pathol., 153, 695–701.
73 Huynh, D.P., Del Bigio, M.R., Ho, D.H. and Pulst, S.M. (1999) Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer’s disease and spinocerebellar ataxia 2. Ann. Neurol., 45, 232–241.[Web of Science][Medline]
74 Kuemmerle, S., Gutekunst, C.A., Klein, A.M., Li, X.J., Li, S.H., Beal, M.F., Hersch, S.M. and Ferrante, R.J. (1999) Huntington aggregates may not predict neuronal death in Huntington’s disease. Ann. Neurol., 46, 842–849.[Web of Science][Medline]
75 Davies, S.W., Turmaine, M., Cozens, B.A., DiFiglia, M., Sharp, A.H., Ross, C.A., Scherzinger, E., Wanker, E.E., Mangiarini, L. and Bates, G.P. (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90, 537–548.[Web of Science][Medline]
76 Sathasivam, K., Hobbs, C., Turmaine, M., Mangiarini, L., Mahal, A., Bertaux, F., Wanker, E.E., Doherty, P., Davies, S.W. and Bates, G.P. (1999) Formation of polyglutamine inclusions in non-CNS tissue. Hum. Mol. Genet., 8, 813–822.
77 Klement, I.A., Skinner, P.J., Kaytor, M.D., Yi, H., Hersch, S.M., Clark, H.B. and Zoghbi, H.Y. (1998) Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell, 95, 41–53.[Web of Science][Medline]
78 Cummings, C.J., Reinstein, E., Sun, Y., Antalffy, B., Jiang, Y.-h., Ciechanover, A., Orr, H.T., Beaudet, A.L. and Zoghbi, H.Y. (1999) Mutation of the E6–AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice. Neuron, 24, 879–892.[Web of Science][Medline]
79 Chai, Y., Koppenhafer, S.L., Shoesmith, S.J., Perez, M.K. and Paulson, H.L. (1999) Evidence for proteasome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro. Hum. Mol. Genet., 8, 673–682.
80 Cummings, C.J., Mancini, M.A., Antalffy, B., DeFranco, D.B., Orr, H.T. and Zoghbi, H.Y. (1998) Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nature Genet., 19, 148–154.[Web of Science][Medline]
81 Chai, Y., Koppenhafer, S.L., Bonini, N.M. and Paulson, H.L. (1999) Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease. J. Neurosci., 19, 10338–10347.
82 Davies, S.W., Turmaine, M., Cozens, B.A., Raza, A.S., Mahal, A., Mangiarini, L. and Bates, G.P. (1999) From neuronal inclusions to neurodegeneration: neuropathological investigation of a transgenic mouse model of Huntington’s disease. Philos. Trans. R. Soc. Lond. B Biol. Sci., 354, 981–989.[Web of Science][Medline]
83 Merry, D.E., Woods, J., Walcott, J., Bish, L., Fischbeck, K.H. and Abel, A. (1999) Characterization of a transgenic model for SBMA. Am. J Hum. Genet., 65(suppl.), A30.
84 Stenoien, D.L., Cummings, C.J., Adams, H.P., Mancini, M.G., Patel, K., DeMartino, G.N., Marcelli, M., Weigel, N.L. and Mancini, M.A. (1999) Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Hum. Mol. Genet., 8, 731–741.
85 Saudou, F., Finkbeiner, S., Devys, D. and Greenberg, M.E. (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell, 95, 55–66.[Web of Science][Medline]
86 Jackson, G.R., Salecker, I., Dong, X., Yao, X., Arnheim, N., Faber, P.W., MacDonald, M.E. and Zipursky, S.L. (1998) Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron, 21, 633–642.[Web of Science][Medline]
87 Warrick, J.M., Paulson, H.L., Gray-Board, G.L., Bui, Q.T., Fischbeck, K.H., Pittman, R.N. and Bonini, N.M. (1998) Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell, 93, 939–949.[Web of Science][Medline]
88 Warrick, J.M., Chan, H.Y., Gray-Board, G.L., Chai, Y., Paulson, H.L. and Bonini, N.M. (1999) Suppression of polyglutamine-mediated neuro- degeneration in Drosophila by the molecular chaperone HSP70. Nature Genet., 23, 425–428.[Web of Science][Medline]
89 Peters, M.F., Nucifora Jr, F.C., Kushi, J., Seaman, H.C., Cooper, J.K., Herring, W.J., Dawson, V.L., Dawson, T.M. and Ross, C.A. (1999) Nuclear targeting of mutant huntingtin increases toxicity. Mol. Cell. Neurosci., 14, 121–128.[Web of Science][Medline]
90 Boutell, J.M., Thomas, P., Neal, J.W., Weston, V.J., Duce, J., Harper, P.S. and Jones, A.L. (1999) Aberrant interactions of transcriptional repressor proteins with the Huntington’s disease gene product, huntingtin. Hum. Mol. Genet., 8, 1647–1655.
91 Skinner, P.J., Koshy, B., Cummings, C., Klement, I.A., Helin, K., Servadio, A., Zoghbi, H.Y. and Orr, H.T. (1997) Ataxin-1 with extra glutamines induces alterations in nuclear matrix-associated structures. Nature, 389, 971–974.[Medline]
92 Kaytor, M.D., Duvick, L.A., Skinner, P.J., Koob, M.D., Ranum, L.P. and Orr, H.T. (1999) Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7. Hum. Mol. Genet., 8, 1657–1664.
93 Perez, M.K., Paulson, H.L., Pendse, S.J., Saionz, S.J., Bonini, N.M. and Pittman, R.N. (1998) Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation. J. Cell Biol., 143, 1457–1470.
94 Koide, R., Kobayashi, S., Shimohata, T., Ikeuchi, T., Maruyama, M., Saito, M., Yamada, M., Takahashi, H. and Tsuji, S. (1999) A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease? Hum. Mol. Genet., 8, 2047–2053.
95 Waragai, M., Lammers, C.H., Takeuchi, S., Imafuku, I., Udagawa, Y., Kanazawa, I., Kawabata, M., Mouradian, M.M. and Okazawa, H. (1999) PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival. Hum. Mol. Genet., 8, 977–987.
96 Lin, X., Antalffy, B., Kang, D., Orr, T. and Zoghbi, H.Y. (2000) Poly- glutamine expansion in ataxin-1 downregulates specific neuronal genes before pathogenic changes in spinocerebellar ataxia type 1. Nature Neurosci., 3, in press.
97 Goldberg, Y.P., Nicholson, D.W., Rasper, D.M., Kalchman, M.A., Koide, H.B., Graham, R.K., Bromm, M., Kazemi-Esfarjani, P., Thornberry, N.A., Vaillancourt, J.P. et al. (1996) Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nature Genet., 13, 442–449.[Web of Science][Medline]
98 Wellington, C.L., Ellerby, L.M., Hackam, A.S., Margolis, R.L., Trifiro, M.A., Singaraja, R., McCutcheon, K., Salvesen, G.S., Propp, S.S., Bromm, M. et al. (1998) Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J. Biol. Chem., 273, 9158–9167.
99 Sanchez, I., Xu, C.J., Juo, P., Kakizaka, A., Blenis, J. and Yuan, J. (1999) Caspase-8 is required for cell death induced by expanded polyglutamine repeats. Neuron, 22, 623–633.[Web of Science][Medline]
100 Ona, V.O., Li, M., Vonsattel, J.P., Andrews, L.J., Khan, S.Q., Chung, W.M., Frey, A.S., Menon, A.S., Li, X.J., Stieg, P.E. et al. (1999) Inhibition of caspase-1 slows disease progression in a mouse model of Huntington’s disease. Nature, 399, 263–267.[Medline]
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D. K. Nag, M. Fasullo, Z. Dong, and A. Tronnes Inverted repeat-stimulated sister-chromatid exchange events are RAD1-independent but reduced in a msh2 mutant Nucleic Acids Res., September 15, 2005; 33(16): 5243 - 5249. [Abstract] [Full Text] [PDF]
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H. Mukai, T. Isagawa, E. Goyama, S. Tanaka, N. F. Bence, A. Tamura, Y. Ono, and R. R. Kopito Formation of morphologically similar globular aggregates from diverse aggregation-prone proteins in mammalian cells PNAS, August 2, 2005; 102(31): 10887 - 10892. [Abstract] [Full Text] [PDF]
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R. D. Wells, R. Dere, M. L. Hebert, M. Napierala, and L. S. Son Advances in mechanisms of genetic instability related to hereditary neurological diseases Nucleic Acids Res., July 8, 2005; 33(12): 3785 - 3798. [Abstract] [Full Text] [PDF]
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K.A. Freed, D.W. Cooper, S.P. Brennecke, and E.K. Moses Detection of CAG repeats in pre-eclampsia/eclampsia using the repeat expansion detection method Mol. Hum. Reprod., July 1, 2005; 11(7): 481 - 487. [Abstract] [Full Text] [PDF]
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 N. G. Faux, S. P. Bottomley, A. M. Lesk, J. A. Irving, J. R. Morrison, M. G. de la Banda, and J. C. Whisstock Functional insights from the distribution and role of homopeptide repeat-containing proteins Genome Res., April 1, 2005; 15(4): 537 - 551. [Abstract] [Full Text] [PDF]
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K. Sobczak and W. J. Krzyzosiak CAG Repeats Containing CAA Interruptions Form Branched Hairpin Structures in Spinocerebellar Ataxia Type 2 Transcripts J. Biol. Chem., February 4, 2005; 280(5): 3898 - 3910. [Abstract] [Full Text] [PDF]
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M. Wojciechowska, A. Bacolla, J. E. Larson, and R. D. Wells The Myotonic Dystrophy Type 1 Triplet Repeat Sequence Induces Gross Deletions and Inversions J. Biol. Chem., January 14, 2005; 280(2): 941 - 952. [Abstract] [Full Text] [PDF]
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 S. Irwin, M. Vandelft, D. Pinchev, J. L. Howell, J. Graczyk, H. T. Orr, and R. Truant RNA association and nucleocytoplasmic shuttling by ataxin-1 J. Cell Sci., January 1, 2005; 118(1): 233 - 242. [Abstract] [Full Text] [PDF]
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V. I. Hashem, M. J. Pytlos, E. A. Klysik, K. Tsuji, M. Khajav, T. Ashizawa, and R. R. Sinden Chemotherapeutic deletion of CTG repeats in lymphoblast cells from DM1 patients Nucleic Acids Res., December 1, 2004; 32(21): 6334 - 6346. [Abstract] [Full Text] [PDF]
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L. M. Pollard, R. Sharma, M. Gomez, S. Shah, M. B. Delatycki, L. Pianese, A. Monticelli, B. J.B. Keats, and S. I. Bidichandani Replication-mediated instability of the GAA triplet repeat mutation in Friedreich ataxia Nucleic Acids Res., November 8, 2004; 32(19): 5962 - 5971. [Abstract] [Full Text] [PDF]
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 S. K. Young, G. M. Taylor, S. Jain, L. M. Suneetha, S. Suneetha, D. N. J. Lockwood, and D. B. Young Microsatellite Mapping of Mycobacterium leprae Populations in Infected Humans J. Clin. Microbiol., November 1, 2004; 42(11): 4931 - 4936. [Abstract] [Full Text] [PDF]
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 P. Astolfi, A. De Pasquale, and L.A. Zonta Late paternity and stillbirth risk Hum. Reprod., November 1, 2004; 19(11): 2497 - 2501. [Abstract] [Full Text] [PDF]
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D. K. Nag, M. Suri, and E. K. Stenson Both CAG repeats and inverted DNA repeats stimulate spontaneous unequal sister-chromatid exchange in Saccharomyces cerevisiae Nucleic Acids Res., October 19, 2004; 32(18): 5677 - 5684. [Abstract] [Full Text] [PDF]
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S. D. Buckingham, B. Esmaeili, M. Wood, and D. B. Sattelle RNA interference: from model organisms towards therapy for neural and neuromuscular disorders Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R275 - R288. [Abstract] [Full Text] [PDF]
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K. Sobczak and W. J. Krzyzosiak Imperfect CAG Repeats Form Diverse Structures in SCA1 Transcripts J. Biol. Chem., October 1, 2004; 279(40): 41563 - 41572. [Abstract] [Full Text] [PDF]
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R. Dere, M. Napierala, L. P. W. Ranum, and R. D. Wells Hairpin Structure-forming Propensity of the (CCTG{middle dot}CAGG) Tetranucleotide Repeats Contributes to the Genetic Instability Associated with Myotonic Dystrophy Type 2 J. Biol. Chem., October 1, 2004; 279(40): 41715 - 41726. [Abstract] [Full Text] [PDF]
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 S. Bhattacharyya and R. S. Lahue Saccharomyces cerevisiae Srs2 DNA Helicase Selectively Blocks Expansions of Trinucleotide Repeats Mol. Cell. Biol., September 1, 2004; 24(17): 7324 - 7330. [Abstract] [Full Text] [PDF]
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E. S. Chevalier-Larsen, C. J. O'Brien, H. Wang, S. C. Jenkins, L. Holder, A. P. Lieberman, and D. E. Merry Castration Restores Function and Neurofilament Alterations of Aged Symptomatic Males in a Transgenic Mouse Model of Spinal and Bulbar Muscular Atrophy J. Neurosci., May 19, 2004; 24(20): 4778 - 4786. [Abstract] [Full Text] [PDF]
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B. O'Nuallain, A. D. Williams, P. Westermark, and R. Wetzel Seeding Specificity in Amyloid Growth Induced by Heterologous Fibrils J. Biol. Chem., April 23, 2004; 279(17): 17490 - 17499. [Abstract] [Full Text] [PDF]
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M. J. Dixon and R. S. Lahue DNA elements important for CAG{middle dot}CTG repeat thresholds in Saccharomyces cerevisiae Nucleic Acids Res., February 24, 2004; 32(4): 1289 - 1297. [Abstract] [Full Text] [PDF]
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C. Savouret, C. Garcia-Cordier, J. Megret, H. te Riele, C. Junien, and G. Gourdon MSH2-Dependent Germinal CTG Repeat Expansions Are Produced Continuously in Spermatogonia from DM1 Transgenic Mice Mol. Cell. Biol., January 15, 2004; 24(2): 629 - 637. [Abstract] [Full Text] [PDF]
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L. Kennedy, E. Evans, C.-M. Chen, L. Craven, P. J. Detloff, M. Ennis, and P. F. Shelbourne Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis Hum. Mol. Genet., December 15, 2003; 12(24): 3359 - 3367. [Abstract] [Full Text] [PDF]
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J. L. Callahan, K. J. Andrews, V. A. Zakian, and C. H. Freudenreich Mutations in Yeast Replication Proteins That Increase CAG/CTG Expansions Also Increase Repeat Fragility Mol. Cell. Biol., November 1, 2003; 23(21): 7849 - 7860. [Abstract] [Full Text] [PDF]
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J. Cocquet, E. De Baere, S. Caburet, and R. A. Veitia Compositional Biases and Polyalanine Runs in Humans Genetics, November 1, 2003; 165(3): 1613 - 1617. [Abstract] [Full Text] [PDF]
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A. Jasinska, G. Michlewski, M. de Mezer, K. Sobczak, P. Kozlowski, M. Napierala, and W. J. Krzyzosiak Structures of trinucleotide repeats in human transcripts and their functional implications Nucleic Acids Res., October 1, 2003; 31(19): 5463 - 5468. [Abstract] [Full Text] [PDF]
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K. Sobczak, M. de Mezer, G. Michlewski, J. Krol, and W. J. Krzyzosiak RNA structure of trinucleotide repeats associated with human neurological diseases Nucleic Acids Res., October 1, 2003; 31(19): 5469 - 5482. [Abstract] [Full Text] [PDF]
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 M B Muzaimi, C M Wiles, N P Robertson, D Ravine, and D A S Compston Task specific focal dystonia: a presentation of spinocerebellar ataxia type 6 J. Neurol. Neurosurg. Psychiatry, October 1, 2003; 74(10): 1444 - 1445. [Full Text] [PDF]
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S. Marchal, E. Shehi, M.-C. Harricane, P. Fusi, F. Heitz, P. Tortora, and R. Lange Structural Instability and Fibrillar Aggregation of Non-expanded Human Ataxin-3 Revealed under High Pressure and Temperature J. Biol. Chem., August 22, 2003; 278(34): 31554 - 31563. [Abstract] [Full Text] [PDF]
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S.-R. Yoon, L. Dubeau, M. de Young, N. S. Wexler, and N. Arnheim Huntington disease expansion mutations in humans can occur before meiosis is completed PNAS, July 22, 2003; 100(15): 8834 - 8838. [Abstract] [Full Text] [PDF]
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J. Xia, D. H. Lee, J. Taylor, M. Vandelft, and R. Truant Huntingtin contains a highly conserved nuclear export signal Hum. Mol. Genet., June 15, 2003; 12(12): 1393 - 1403. [Abstract] [Full Text] [PDF]
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T. Nenguke, M. I. Aladjem, J. F. Gusella, N. S. Wexler, The Venezuela HD Project, and N. Arnheim Candidate DNA replication initiation regions at human trinucleotide repeat disease loci Hum. Mol. Genet., May 1, 2003; 12(9): 1021 - 1028. [Abstract] [Full Text] [PDF]
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T. Okuda, H. Hattori, S. Takeuchi, J. Shimizu, H. Ueda, J. J. Palvimo, I. Kanazawa, H. Kawano, M. Nakagawa, and H. Okazawa PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype Hum. Mol. Genet., April 1, 2003; 12(7): 711 - 725. [Abstract] [Full Text] [PDF]
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B. L. Heidenfelder, A. M. Makhov, and M. D. Topal Hairpin Formation in Friedreich's Ataxia Triplet Repeat Expansion J. Biol. Chem., January 17, 2003; 278(4): 2425 - 2431. [Abstract] [Full Text] [PDF]
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A. K. Thakur and R. Wetzel Mutational analysis of the structural organization of polyglutamine aggregates PNAS, December 24, 2002; 99(26): 17014 - 17019. [Abstract] [Full Text] [PDF]
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J. L. Walcott and D. E. Merry Ligand Promotes Intranuclear Inclusions in a Novel Cell Model of Spinal and Bulbar Muscular Atrophy J. Biol. Chem., December 20, 2002; 277(52): 50855 - 50859. [Abstract] [Full Text] [PDF]
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W. Yang, J. R. Dunlap, R. B. Andrews, and R. Wetzel Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells Hum. Mol. Genet., November 1, 2002; 11(23): 2905 - 2917. [Abstract] [Full Text] [PDF]
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C. E. Pearson, M. Tam, Y.-H. Wang, S. E. Montgomery, A. C. Dar, J. D. Cleary, and K. Nichol Slipped-strand DNAs formed by long (CAG){middle dot}(CTG) repeats: slipped-out repeats and slip-out junctions Nucleic Acids Res., October 15, 2002; 30(20): 4534 - 4547. [Abstract] [Full Text] [PDF]
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U. M. Lindstrom and E. T. Kool An orthogonal oligonucleotide protecting group strategy that enables assembly of repetitive or highly structured DNAs Nucleic Acids Res., October 1, 2002; 30(19): e101 - e101. [Abstract] [Full Text] [PDF]
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S. Bhattacharyya, M. L. Rolfsmeier, M. J. Dixon, K. Wagoner, and R. S. Lahue Identification of RTG2 as a Modifier Gene for CTG{middle dot}CAG Repeat Instability in Saccharomyces cerevisiae Genetics, October 1, 2002; 162(2): 579 - 589. [Abstract] [Full Text] [PDF]
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M. J. Bennett, K. E. Huey-Tubman, A. B. Herr, A. P. West Jr., S. A. Ross, and P. J. Bjorkman Inaugural Article: A linear lattice model for polyglutamine in CAG-expansion diseases PNAS, September 3, 2002; 99(18): 11634 - 11639. [Abstract] [Full Text] [PDF]
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S. Chen, F. A. Ferrone, and R. Wetzel Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation PNAS, September 3, 2002; 99(18): 11884 - 11889. [Abstract] [Full Text] [PDF]
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E. Fabre, B. Dujon, and G.-F. Richard Transcription and nuclear transport of CAG/CTG trinucleotide repeats in yeast Nucleic Acids Res., August 15, 2002; 30(16): 3540 - 3547. [Abstract] [Full Text] [PDF]
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K. Nichol and a. C. E. Pearson CpG Methylation Modifies the Genetic Stability of Cloned Repeat Sequences Genome Res., August 1, 2002; 12(8): 1246 - 1256. [Abstract] [Full Text] [PDF]
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J. Brohede, C. R. Primmer, A. Moller, and H. Ellegren Heterogeneity in the rate and pattern of germline mutation at individual microsatellite loci Nucleic Acids Res., May 1, 2002; 30(9): 1997 - 2003. [Abstract] [Full Text] [PDF]
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G. B. Panigrahi, J. D. Cleary, and C. E. Pearson In Vitro (CTG){middle dot}(CAG) Expansions and Deletions by Human Cell Extracts J. Biol. Chem., April 12, 2002; 277(16): 13926 - 13934. [Abstract] [Full Text] [PDF]
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Y. Zhang, D. G. Monckton, M. J. Siciliano, T. H. Connor, and M. L. Meistrich Age and insertion site dependence of repeat number instability of a human DM1 transgene in individual mouse sperm Hum. Mol. Genet., April 1, 2002; 11(7): 791 - 798. [Abstract] [Full Text] [PDF]
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N. J. Caplen, J. P. Taylor, V. S. Statham, F. Tanaka, A. Fire, and R. A. Morgan Rescue of polyglutamine-mediated cytotoxicity by double-stranded RNA-mediated RNA interference Hum. Mol. Genet., January 1, 2002; 11(2): 175 - 184. [Abstract] [Full Text] [PDF]
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S. E. Corrette-Bennett, N. L. Mohlman, Z. Rosado, J. J. Miret, P. M. Hess, B. O. Parker, and R. S. Lahue Efficient repair of large DNA loops in Saccharomyces cerevisiae Nucleic Acids Res., October 15, 2001; 29(20): 4134 - 4143. [Abstract] [Full Text] [PDF]
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R. I. Richards Dynamic mutations: a decade of unstable expanded repeats in human genetic disease Hum. Mol. Genet., October 1, 2001; 10(20): 2187 - 2194. [Abstract] [Full Text] [PDF]
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A. E. Bevivino and P. J. Loll An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel beta -fibrils PNAS, September 19, 2001; (2001) 211305198. [Abstract] [Full Text] [PDF]
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N.L. Dean, S.L. Tan, and A. Ao The development of preimplantation genetic diagnosis for myotonic dystrophy using multiplex fluorescent polymerase chain reaction and its clinical application Mol. Hum. Reprod., September 1, 2001; 7(9): 895 - 901. [Abstract] [Full Text] [PDF]
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S. Temnykh, G. DeClerck, A. Lukashova, L. Lipovich, S. Cartinhour, and S. McCouch Computational and Experimental Analysis of Microsatellites in Rice (Oryza sativa L.): Frequency, Length Variation, Transposon Associations, and Genetic Marker Potential Genome Res., August 1, 2001; 11(8): 1441 - 1452. [Abstract] [Full Text] [PDF]
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B. O. Evert, I. R. Vogt, C. Kindermann, L. Ozimek, R. A. I. de Vos, E. R. P. Brunt, I. Schmitt, T. Klockgether, and U. Wullner Inflammatory Genes Are Upregulated in Expanded Ataxin-3-Expressing Cell Lines and Spinocerebellar Ataxia Type 3 Brains J. Neurosci., August 1, 2001; 21(15): 5389 - 5396. [Abstract] [Full Text] [PDF]
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K. Nakamura, S.-Y. Jeong, T. Uchihara, M. Anno, K. Nagashima, T. Nagashima, S.-i. Ikeda, S. Tsuji, and I. Kanazawa SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein Hum. Mol. Genet., July 1, 2001; 10(14): 1441 - 1448. [Abstract] [Full Text] [PDF]
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C. J. Cummings, Y. Sun, P. Opal, B. Antalffy, R. Mestril, H. T. Orr, W. H. Dillmann, and H. Y. Zoghbi Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice Hum. Mol. Genet., July 1, 2001; 10(14): 1511 - 1518. [Abstract] [Full Text] [PDF]
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A. L. Peel, R. V. Rao, B. A. Cottrell, M. R. Hayden, L. M. Ellerby, and D. E. Bredesen Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington's disease (HD) transcripts and is activated in HD tissue Hum. Mol. Genet., July 1, 2001; 10(15): 1531 - 1538. [Abstract] [Full Text] [PDF]
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M. Gomes-Pereira, M. T. Fortune, and D. G. Monckton Mouse tissue culture models of unstable triplet repeats: in vitro selection for larger alleles, mutational expansion bias and tissue specificity, but no association with cell division rates Hum. Mol. Genet., April 1, 2001; 10(8): 845 - 854. [Abstract] [Full Text] [PDF]
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M. L. Rolfsmeier, M. J. Dixon, L. Pessoa-Brandão, R. Pelletier, J. J. Miret, and R. S. Lahue Cis-Elements Governing Trinucleotide Repeat Instability in Saccharomyces cerevisiae Genetics, April 1, 2001; 157(4): 1569 - 1579. [Abstract] [Full Text]
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H. Awata, C. Huang, M. E. Handlogten, and R. T. Miller Interaction of the Calcium-sensing Receptor and Filamin, a Potential Scaffolding Protein J. Biol. Chem., September 7, 2001; 276(37): 34871 - 34879. [Abstract] [Full Text] [PDF]
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E. A. Oussatcheva, V. I. Hashem, Y. Zou, R. R. Sinden, and V. N. Potaman Involvement of the Nucleotide Excision Repair Protein UvrA in Instability of CAG{middle dot}CTG Repeat Sequences in Escherichia coli J. Biol. Chem., August 10, 2001; 276(33): 30878 - 30884. [Abstract] [Full Text] [PDF]
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A. E. Bevivino and P. J. Loll An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel beta -fibrils PNAS, October 9, 2001; 98(21): 11955 - 11960. [Abstract] [Full Text] [PDF]
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