Journal
TRENDS IN CELL BIOLOGY
Volume 19, Issue 5, Pages 207-217Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tcb.2009.03.001
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Funding
- Human Frontiers Science Program Organization (HSFPO-LTF award)
- Netherlands Organization for Scientific Research (NWO-VIDI grant)
- Swiss Cancer League
- Novartis Research Foundation
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Chromatin structure has a crucial role in processes of metabolism, including transcription, DNA replication and DNA damage repair. An evolutionarily conserved variant of histone H2A, called H2AX, is one of the key components of chromatin. H2AX becomes rapidly phosphorylated on chromatin surrounding DNA double-strand breaks (DSBs). Recent studies have shown that H2AX and other components of damaged chromatin also become modified by acetylation and ubiquitylation. This review discusses how specific combinations of histone modifications affect the accumulation and function of DNA repair factors (MDC1, RNF8, RNF168, 53BP1, BRCA1) and chromatin remodeling complexes (INO80, SWR1, TIP60-p400) at DSBs. These collectively regulate DSB repair and checkpoint arrest, avoiding genomic instability and oncogenic transformation in higher eukaryotes.
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