What histone code for DNA repair?

Abstract

Chromatin structure plays a key role in most processes involving DNA metabolism. Chromatin modifications implicated in transcriptional regulation are relatively well characterized and are thought to be the result of a code on the histone proteins (histone code). This code, involving phosphorylation, ubiquitylation, sumoylation, acetylation and methylation, is believed to regulate chromatin accessibility either by disrupting chromatin contacts or by recruiting non-histone proteins to chromatin. Recent evidences suggest that such mechanisms are also involved in DNA damage detection and DNA repair. One of the most well-characterized modifications is caused by the formation of DNA double strand breaks (DSBs), resulting in phosphorylation of histone H2AX (the so-called gamma-H2AX) on the chromatin surrounding the DNA lesion. It is generally believed that histone H2AX phosphorylation is required for the concentration and stabilization of DNA repair proteins to the damaged chromatin. The phosphorylation of this histone seems to play a role in both non-homologous end-joining (NHEJ) and homologous recombination (HR) repair pathways. However, the choice of the repair pathway might depend on or induce additional post-translational modifications affecting other histone proteins necessary to the completion of the entire DNA repair process. Interestingly, even in the absence of DSBs, histone modifications occur. Indeed, following UV-exposure, histone acetylation takes place and is believed to facilitate the nucleotide excision repair (NER) process by promoting chromatin accessibility to the repair factors. This review focuses on recent data characterizing the function of histone modification in various repair processes and discusses if the combination of such modifications can be the trademark of a specific DNA repair pathway.