Human Molecular Genetics Advance Access published online on December 1, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddi027
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 DNA Repair Team, International Agency for Research on Cancer, 150 cours Albert Thomas, Lyon, 69372, France; Laboratoire "Protéines du Cytosquelette", Institut de Biologie Structurale, 41, rue Jules Horowitz, 38027 Grenoble cedex 1
* To whom correspondence should be addressed. Ten new patients with the Ataxia telangiectasia-like disorder, ATLD, from three unrelated Saudi Arabian families have been identified aged 5 to 37 representing the largest cohort of ATLD patients ever identified. They presented with an early onset, slowly progressive, ataxia plus ocular apraxia phenotype with an absence of tumour development, even in the oldest patient. Extra-neurological features such as telangiectasia, raised alpha-foetoprotein and reduced immunoglobulin levels were absent. No translocations were found in the two investigated patients and the presence of microcephaly was noted in four out of eight ascertained patients. All patients are homozygous for a novel missense mutation (630G
Article
Identification and functional consequences of a novel MRE11 mutation affecting ten Saudi Arabian patients with the Ataxia telangiectasia-like disorder (ATLD)
2 Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), Illkirch - Strasbourg, 67404, France; Service de Génétique et de Cytogénétique, Hôpital Universitaire Farhat Hached, Sousse, Tunisia
3 Division of Paediatric Neurology, Department of Paediatrics, College of Medicine, King Saud University, Riyadh, 11461
4 Department of Paediatrics, Security Forces Hospital, Riyadh, 11481, Saudi Arabia
5 DNA Repair Team, International Agency for Research on Cancer, 150 cours Albert Thomas, Lyon, 69372, France
6 Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), Illkirch - Strasbourg, 67404, France
Janet Hall, E-mail: hall{at}iarc.fr
Abstract 
C, W210C) of the MRE11 gene. The cellular consequences of this amino acid change, localised in the nuclease domain of the Mre11 protein, have been determined in fibroblast cultures established from two individuals. They showed high constitutive levels of Mre11 and Rad50 proteins compared to cells from normal individuals but a very low level of the Nbs1 protein. After exposure to ionising radiation, a dose-dependent defect in ATM-serine1981, p53-serine15 and Chk2 phosphorylation, and p53 stabilisation were noted, together with a failure to form Mre11 foci and enhanced radiation sensitivity. Formation of 
H2AX foci was similar to that seen in normal fibroblasts under the experimental conditions examined. These results emphasise the importance of functional interactions between the three proteins of the Mre11-Rad50-Nbs1 complex and lend support to a role of this complex as a sensor of DNA double strand breaks, acting upstream of ATM.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Anheim, B. Monga, M. Fleury, P. Charles, C. Barbot, M. Salih, J. P. Delaunoy, M. Fritsch, L. Arning, M. Synofzik, et al. Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients Brain, October 1, 2009; 132(10): 2688 - 2698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Porter-Goff and N. Rhind The Role of MRN in the S-Phase DNA Damage Checkpoint Is Independent of Its Ctp1-dependent Roles in Double-Strand Break Repair and Checkpoint Signaling Mol. Biol. Cell, April 1, 2009; 20(7): 2096 - 2107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kotnis, L. Du, C. Liu, S. W Popov, and Q. Pan-Hammarstrom Non-homologous end joining in class switch recombination: the beginning of the end Phil Trans R Soc B, March 12, 2009; 364(1517): 653 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Heikkinen, K. Rapakko, S.-M. Karppinen, H. Erkko, S. Knuutila, T. Lundan, A. Mannermaa, A.-L. Borresen-Dale, A. Borg, R. B. Barkardottir, et al. RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability Carcinogenesis, August 1, 2006; 27(8): 1593 - 1599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M R Taylor and P J Byrd Molecular pathology of ataxia telangiectasia J. Clin. Pathol., October 1, 2005; 58(10): 1009 - 1015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Brem and J. Hall XRCC1 is required for DNA single-strand break repair in human cells Nucleic Acids Res., May 2, 2005; 33(8): 2512 - 2520. [Abstract] [Full Text] [PDF]
|
|