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Clin Cancer Res. 2010 Sep 15;16(18):4543-52. doi: 10.1158/1078-0432.CCR-10-0513. Epub 2010 Sep 7.

Epigenetic modifications in double-strand break DNA damage signaling and repair.

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1
Laval University Cancer Research Center, Hôtel-Dieu de Québec, Quebec City, Canada.

Abstract

Factors involved in the cellular response to double-strand break (DSB) DNA damage have been identified as potential therapeutic targets that would greatly sensitize cancer cells to radiotherapy and genotoxic chemotherapy. These targets could disable the repair machinery and/or reinstate normal cell-cycle checkpoint leading to growth arrest, senescence, and apoptosis. It is now clear that a major aspect of the DNA damage response occurs through specific interactions with chromatin structure and its modulation. It implicates highly dynamic posttranslational modifications of histones that are critical for DNA damage recognition and/or signaling, repair of the lesion, and release of cell-cycle arrest. Therefore, drugs that target the enzymes responsible for these modifications, or the protein modules reading them, have very high therapeutic potential. This review presents the current state of knowledge on the different chromatin modifications and their roles in each step of eukaryotic DSB DNA damage response.

PMID:
20823147
PMCID:
PMC2940951
DOI:
10.1158/1078-0432.CCR-10-0513
[Indexed for MEDLINE]
Free PMC Article
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