Regulation of DNA repair mechanisms: How the chromatin environment regulates the DNA damage response

Abstract

Cellular DNA is constantly challenged by damage-inducing factors derived from exogenous or endogenous sources. In order to maintain genome stability and integrity, cells have evolved a wide variety of DNA repair pathways which counteract different types of DNA lesions, also referred to as the DNA damage response (DDR). However, DNA in eukaryotes is highly organized and compacted into chromatin representing major constraints for all cellular pathways, including DNA repair pathways, which require DNA as their substrate. Therefore, the chromatin configuration surrounding the lesion site undergoes dramatic remodeling to facilitate access of DNA repair factors and subsequent removal of the DNA lesion. In this review, we focus on the question of how the cellular DNA repair pathways overcome the chromatin barrier, how the chromatin environment is rearranged to facilitate efficient DNA repair, which proteins mediate this re-organization process and, consequently, how the altered chromatin landscape is involved in the regulation of DNA damage responses.