Title: Chromatin Remodeling in DNA Damage Response and Human Aging
Abstract: Chromatin consists of the DNA and all proteins involved in organizing and regulating DNA structure. The building block of chromatin is the nucleosome, which is composed of 146 base pairs of DNA and a core histone octamer. The core histone oactomer is composed of two heterodimers of histone H2A and histone H2B and a tetramer of histone H3 and histone H4 [1]. The overall chromatin structure is very dynamic in response to diverse biological events. Regulation of chromatin structure is achieved by two major mechanisms. The first is post‐ translational modification (PTM) of histones and other chromatin proteins via phosphoryla‐ tion, methylation, acetylation, ubiquitination and sumoylation [2, 3]. The second is through ATP-dependent nucleosome structure alteration. Cooperation between histone PTMs and chromatin remodelers allows chromatin remodeling to regulate diverse biological events including transcription, chromosome segregation, DNA replication, and DNA repair. In this chapter, we summarize how chromatin structure is regulated during DNA damage response (DDR), focusing particularly on three PTMs: phosphorylation, Poly(ADP-ribosyl)ation (PARylation) and sumoylation. We discuss the DDR in a highly compacted chromatic structure, heterochromatin, as well as the interplay between chromatin remodeling, DNA damage and human aging.