Reshaping chromatin after DNA damage: the choreography of histone proteins

Abstract

DNA damage signaling and repair machineries operate in a nuclear environment where DNA is wrapped around histone proteins and packaged into chromatin. Understanding how chromatin structure is restored together with the DNA sequence during DNA damage repair has been a topic of intense research. Indeed, chromatin integrity is central to cell functions and identity. However, chromatin shows remarkable plasticity in response to DNA damage. This review presents our current knowledge of chromatin dynamics in the mammalian cell nucleus in response to DNA double strand breaks and UV lesions. I provide an overview of the key players involved in regulating histone dynamics in damaged chromatin regions, focusing on histone chaperones and their concerted action with histone modifiers, chromatin remodelers and repair factors. I also discuss how these dynamics contribute to reshaping chromatin and, by altering the chromatin landscape, may affect the maintenance of epigenetic information.

Keywords: chromatin remodeling; genotoxic stress; histone chaperones; histone modifications; histone variants.

Fig. 1

Role of histone modifying enzymes and remodeling factors in histone dynamics in response to DNA damage (DSBs or UV lesions). DNA damage-induced histone modifications (red) by acetylation (Ac) and ubiquitylation (Ub) promote nucleosome destabilization, and acetylation may drive histones to proteosomal degradation. The indicated nucleosome remodelers (orange) are involved in histone exchange, nucleosome sliding and/or disruption with histone eviction from damaged chromatin. Displaced histones may be re-positioned/re-deposited after repair of DNA damage. The contribution of remodelers to chromatin restoration is still to be determined.

Fig. 2

Role of histone chaperones in histone dynamics in response to DNA damage (DSBs or UV lesions). Nucleosome disorganization after DNA damage is followed by nucleosome re-assembly with de novo histone deposition and potential recycling of displaced histones. The indicated histone chaperones promote histone exchange, histone eviction and de novo deposition in damaged chromatin. ASF1, known to act both as a histone donor and acceptor, may facilitate the recycling of displaced histones by coupling nucleosome disassembly and re-assembly.