The Influence of Chromatin Domains on the Repair of Double-Strand Breaks

Abstract

Double-strand breaks (DSBs) represent particularly dangerous forms of DNA damage that can result in the formation of mutations and chromosomal rearrangements when unrepaired or misrepaired. In order to preserve genome integrity, DSBs can be processed and repaired through several pathways, including homologous recombination (HR) and non-homologous end joining (NHEJ). As the final repair products depend on the pathway utilized to restore the damage, the process of repair pathway choice constitutes a crucial step of DSB repair. In eukaryotes, chromatin is classified into two main domains, euchromatin and heterochromatin, each exhibiting differences in protein composition and function. While both euchromatin and heterochromatin can be subjected to DSB formation, it has recently been proposed that the chromatin environment surrounding the DSB site might contribute to the repair pathway choice process. Both pre-existing and damage-induced histone marks, histone variants and chromatin associated proteins of euchromatin and heterochromatin have been found to be involved in several steps of DSB repair in their respective domains, including the selective recruitment of certain repair proteins to promote the usage of specific repair pathways. This suggests that the role of euchromatin- or heterochromatin- proteins during DSB repair is to promote the usage of repair pathways that suit best the characteristics of their respective domains. Here, we discuss the influence of chromatin components on DSB repair. More specifically, we will focus on the roles covered by histone marks, histone variants and non-histone proteins associated with euchromatin and heterochromatin in different steps of DSB repair.