Distribution and Dynamics of Chromatin Modification Induced by a Defined DNA Double-Strand Break

Abstract

Both Mec1p and Tel1p can respond to a DSB, with distinct roles for these checkpoint kinases at different phases of the cell cycle. Part of this response involves histone phosphorylation over large chromosomal domains; however, the distinct distributions of gamma-H2AX and repair proteins near DSBs indicate that localization of repair proteins to breaks is not likely to be the main function of this histone modification.

The ubiquitin landscape at DNA double-strand breaks

“…During DSB repair, there is a clearing of -H2AX and nucleosomes directly adjacent to the DSB (Shroff et al, 2004;Berkovich et al, 2007). These dechromatinized regions are thought to be the site of the majority of DSB repair chemistry.…”

Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

“…Phosphorylation of H2AX ("γ-H2AX") is a rapid, evolutionarily conserved event in the DSB response of eukaryotes and marks chromatin for hundreds of kilobases flanking the DSB [129]. H2AX contributes to DSBR, including SCR, by mechanisms that may involve cohesin complexes [46][47][48]130,131].…”

Chromatin dynamics coupled to DNA repair

“…This in turn results in accumulation of more repair factors, which function as mediators and effectors. Using chromatin immunoprecipitation (ChIP) assays, phosphorylated H2AX can be detected over 50 kb in yeast, 35 or 1-2 Mb in mammalian cells 24 surrounding the DNA lesions. These γH2AX domains form discrete nuclear foci, which can be detected by immunofluorescence microscopy with antibodies against γH2AX.…”

“…In contrast, Mre11 and other DNA repair proteins are enriched solely at DSB-flanking sites and decrease rapidly with distance, and thus in inverse relationship to levels of γH2AX. 35,95,96 It has become important to determine the remodeling activities that might be involved in the reorganization of chromatin and the complex crosstalk between them that ensures the proper recruitment of DNA-repair proteins and the effective repair of DNA lesions.…”