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PMID: 21056014 Published · ppublish English Journal Article Review

The ubiquitous role of ubiquitin in the DNA damage response.

DNA repair ·Vol. 9 ·No. 12 ·2010-12-10 ·Pages 1229-40

Al-Hakim A, Escribano-Diaz C, Landry MC, O'Donnell L, Panier S, Szilard RK, Durocher D

Abstract

Protein ubiquitylation has emerged as an important regulatory mechanism that impacts almost every aspect of the DNA damage response. In this review, we discuss how DNA repair and checkpoint pathways utilize the diversity offered by the ubiquitin conjugation system to modulate the response to genotoxic lesions in space and time. In particular, we will highlight recent work done on the regulation of DNA double-strand breaks signalling and repair by the RNF8/RNF168 E3 ubiquitin ligases, the Fanconi anemia pathway and the role of protein degradation in the enforcement and termination of checkpoint signalling. We also discuss the various functions of deubiquitylating enzymes in these processes along with potential avenues for exploiting the ubiquitin conjugation/deconjugation system for therapeutic purposes.

MeSH Terms
DNA Breaks, Double-Stranded DNA Repair/genetics,physiology DNA-Binding Proteins/metabolism Fanconi Anemia Complementation Group Proteins/metabolism Genes, cdc/physiology Proteasome Endopeptidase Complex/metabolism Signal Transduction/genetics,physiology Ubiquitin/metabolism Ubiquitin-Protein Ligases/metabolism
Chemicals
DNA-Binding Proteins Fanconi Anemia Complementation Group Proteins RNF8 protein, human Ubiquitin RNF168 protein, human Ubiquitin-Protein Ligases Proteasome Endopeptidase Complex
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Al-Hakim Abdallah
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, M5G 1X5, ON, Canada.
Escribano-Diaz Cristina
Landry Marie-Claude
O'Donnell Lara
Panier Stephanie
Szilard Rachel K
Durocher Daniel
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Article Info
Journal
DNA repair
Abbr.
DNA Repair (Amst)
ISSN
1568-7856
DOI
10.1016/j.dnarep.2010.09.011
Published
2010-12-10
Epub
2010-00-04
Pages
1229-40
Language
English
Region
Netherlands
NLM ID
101139138
PMCID
PMC7105183
Subset
IM
External Links
PubMed source DOI: 10.1016/j.dnarep.2010.09.011 PMC Full Text View journal details
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