Role of Histone Methylation in Maintenance of Genome Integrity.

Arjamand Mushtaq,Mohammad Altaf,Clayton R Hunt,Wajahat W Tantray,Audesh Bhat,Ulfat Syed Mir,Tej K Pandita,Shruti Pandita,Raj K Pandita

doi:10.3390/genes12071000

Abstract

Packaging of the eukaryotic genome with histone and other proteins forms a chromatin structure that regulates the outcome of all DNA mediated processes. The cellular pathways that ensure genomic stability detect and repair DNA damage through mechanisms that are critically dependent upon chromatin structures established by histones and, particularly upon transient histone post-translational modifications. Though subjected to a range of modifications, histone methylation is especially crucial for DNA damage repair, as the methylated histones often form platforms for subsequent repair protein binding at damaged sites. In this review, we highlight and discuss how histone methylation impacts the maintenance of genome integrity through effects related to DNA repair and repair pathway choice.

Highlights

The packaging of eukaryotic DNA with histone proteins forms the fundamental unit of chromatin called the nucleosome
H4K20 methylation levels do not change upon DNA damage, but the preexisting H4K20me becomes exposed and assists repair protein recruitment to the damage site [20,21]
Histone H4 lysine 20 methylation is the only reported methylation site on H4 that has a role in maintaining genome integrity upon DNA damage [19]

Summary

Introduction

The packaging of eukaryotic DNA with histone proteins forms the fundamental unit of chromatin called the nucleosome. It is important that cells identify the breaks and initiate and activate processes to repair the damaged DNA [6,7]. Histone proteins undergo various post-translational modifications (PTMs), such as phosphorylation, acetylation, methylation, ubiquitylation, and sumoylation [1,2] These modifications influence chromatin structure by altering histone DNA interactions, and by acting as docking sites for various proteins to regulate essential aspects of DNA-dependent transactions [1,2]. Histone modifications help to sense DNA damage, facilitate recruitment of repair factors to the break site, and re-establish a normal chromatin structure after repair (Figure 1) [16]. Ferases (HATs) and recruits various DSB-repair and chromatin-modifying proteins Binding of these proteins, such as 523.BHPiHst1ois,ntoeNnHeu4HKA4204lyM,sianetenh2yd0lamPtioe4nth0iy0nla,DtiloNenAaidsRteshpeatioornlDy rSeBporrteedpmaeitrhyfloatliloonwsitee donbHy4 tchhatromatin compaction, which helps in maihnatsaairnolieningmgaeinntaoinmingegiennotemge rinitteyg.rity upon DNA damage [19]. H4K20 methylation plays a prominent role in NHEJ by serving as a binding site for 53BP1 at damage sites, which stimulates a downstream cascade involving

Histone H4K20 Methylation in DNA Repair

Histone H3K4 Methylation in DNA Repair

H3K36 Methylation in the DNA Damage Response