Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (31)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Rapic-Otrin, V.
Right arrow Articles by Stefanini, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rapic-Otrin, V.
Right arrow Articles by Stefanini, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2003, Vol. 12, No. 13 1507-1522
DOI: 10.1093/hmg/ddg174
© 2003 Oxford University Press

True XP group E patients have a defective UV-damaged DNA binding protein complex and mutations in DDB2 which reveal the functional domains of its p48 product

Vesna Rapic-Otrin1,{dagger}, Valentina Navazza2,{dagger}, Tiziana Nardo2, Elena Botta2, Mary McLenigan3, Dawn C. Bisi1, Arthur S. Levine1,* and Miria Stefanini2

1Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA, 2Istituto di Genetica Molecolare CNR, Via Abbiategrasso, 207-27100 Pavia, Italy and 3Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-2725, USA

Received February 14, 2003; Revised May 2, 2003; Accepted May 7, 2003

Xeroderma pigmentosum (XP) is a skin cancer-prone autosomal recessive disease characterized by inability to repair UV-induced DNA damage. The major form of XP is defective in nucleotide excision repair (NER) and comprises seven complementation groups (A–G). The genes defective in all groups have been identified unambiguously with the exception of group E. The cells of some XP-E patients are deficient in a protein complex (consisting of two subunits: p127/DDBI and p48/DDB2) which binds to UV-damaged DNA (UV-DDB) and is specifically involved in the removal of photoproducts from the non-transcribed regions of the genome. However, other XP-E patients have been reported not to lack UV-damaged DNA binding activity (DDB+). Here we describe several genetically unrelated XP-E patients, not previously analyzed in depth, each carrying two mutated alleles for DDB2, causing either a single amino acid change or a protein truncation or internal deletion. These defects result in a severe decrease of detectable p48 protein, abolish interaction with the p127 subunit, and produce a deficiency in UV-DDB binding activity (DDB-). The role of p48 in the repair defect of these patients was demonstrated in vivo and in vitro. Investigation of four DDB+ cell strains from patients previously assigned to XP-E, allowed us to reclassify all of them into other groups and to show that they do not share the molecular and biochemical features typical for XP-E. Besides confirming that the true XP-E phenotype is DDB-, resulting from defects in a single gene, DDB2, our results identify the functional domains of the corresponding p48 protein.

* To whom correspondence should be addressed at: University of Pittsburgh, Scaife Hall, Suite 401, 3550 Terrace Street, Pittsburgh, PA 15261, USA. Tel: +1 4126488975; Fax: +1 4126481236; Email: alevine{at}hs.pitt.edu

{dagger} The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
J. Guerrero-Santoro, M. G. Kapetanaki, C. L. Hsieh, I. Gorbachinsky, A. S. Levine, and V. Rapic-Otrin
The Cullin 4B-Based UV-Damaged DNA-Binding Protein Ligase Binds to UV-Damaged Chromatin and Ubiquitinates Histone H2A
Cancer Res., July 1, 2008; 68(13): 5014 - 5022.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
P Vahteristo, A Kokko, O Saksela, K Aittomaki, and L A Aaltonen
Blood-derived gene-expression profiling in unravelling susceptibility to recessive disease
J. Med. Genet., November 1, 2007; 44(11): 718 - 720.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Q.-E. Wang, M. Praetorius-Ibba, Q. Zhu, M. A. El-Mahdy, G. Wani, Q. Zhao, S. Qin, S. Patnaik, and A. A. Wani
Ubiquitylation-independent degradation of Xeroderma pigmentosum group C protein is required for efficient nucleotide excision repair
Nucleic Acids Res., August 13, 2007; 35(16): 5338 - 5350.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. S. Luijsterburg, J. Goedhart, J. Moser, H. Kool, B. Geverts, A. B. Houtsmuller, L. H. F. Mullenders, W. Vermeulen, and R. van Driel
Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC
J. Cell Sci., August 1, 2007; 120(15): 2706 - 2716.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
E. Pick, O.-S. Lau, T. Tsuge, S. Menon, Y. Tong, N. Dohmae, S. M. Plafker, X. W. Deng, and N. Wei
Mammalian DET1 Regulates Cul4A Activity and Forms Stable Complexes with E2 Ubiquitin-Conjugating Enzymes
Mol. Cell. Biol., July 1, 2007; 27(13): 4708 - 4719.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. Marini, T. Nardo, M. Giannattasio, M. Minuzzo, M. Stefanini, P. Plevani, and M. M. Falconi
DNA nucleotide excision repair-dependent signaling to checkpoint activation
PNAS, November 14, 2006; 103(46): 17325 - 17330.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. A. Lovejoy, K. Lock, A. Yenamandra, and D. Cortez
DDB1 Maintains Genome Integrity through Regulation of Cdt1
Mol. Cell. Biol., November 1, 2006; 26(21): 7977 - 7990.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
Y. J. He, C. M. McCall, J. Hu, Y. Zeng, and Y. Xiong
DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases.
Genes & Dev., November 1, 2006; 20(21): 2949 - 2954.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Li, Q.-E. Wang, Q. Zhu, M. A. El-Mahdy, G. Wani, M. Praetorius-Ibba, and A. A. Wani
DNA Damage Binding Protein Component DDB1 Participates in Nucleotide Excision Repair through DDB2 DNA-binding and Cullin 4A Ubiquitin Ligase Activity.
Cancer Res., September 1, 2006; 66(17): 8590 - 8597.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
N. Suka, E. Nakashima, K. Shinmyozu, M. Hidaka, and H. Jingami
The WD40-repeat protein Pwp1p associates in vivo with 25S ribosomal chromatin in a histone H4 tail-dependent manner
Nucleic Acids Res., July 19, 2006; 34(12): 3555 - 3567.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. A. El-Mahdy, Q. Zhu, Q.-e. Wang, G. Wani, M. Praetorius-Ibba, and A. A. Wani
Cullin 4A-mediated Proteolysis of DDB2 Protein at DNA Damage Sites Regulates in Vivo Lesion Recognition by XPC
J. Biol. Chem., May 12, 2006; 281(19): 13404 - 13411.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. G. Kapetanaki, J. Guerrero-Santoro, D. C. Bisi, C. L. Hsieh, V. Rapic-Otrin, and A. S. Levine
The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites
PNAS, February 21, 2006; 103(8): 2588 - 2593.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. O. Wittschieben, S. Iwai, and R. D. Wood
DDB1-DDB2 (Xeroderma Pigmentosum Group E) Protein Complex Recognizes a Cyclobutane Pyrimidine Dimer, Mismatches, Apurinic/Apyrimidinic Sites, and Compound Lesions in DNA
J. Biol. Chem., December 2, 2005; 280(48): 39982 - 39989.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Alekseev, H. Kool, H. Rebel, M. Fousteri, J. Moser, C. Backendorf, F. R. de Gruijl, H. Vrieling, and L. H.F. Mullenders
Enhanced DDB2 Expression Protects Mice from Carcinogenic Effects of Chronic UV-B Irradiation
Cancer Res., November 15, 2005; 65(22): 10298 - 10306.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Itoh, D. Cado, R. Kamide, and S. Linn
DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen
PNAS, February 17, 2004; 101(7): 2052 - 2057.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.