Chromatin plasticity in response to DNA damage: The shape of things to come - PubMed (original) (raw)

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Chromatin plasticity in response to DNA damage: The shape of things to come

Salomé Adam et al. DNA Repair (Amst). 2015 Aug.

Abstract

DNA damage poses a major threat to cell function and viability by compromising both genome and epigenome integrity. The DNA damage response indeed operates in the context of chromatin and relies on dynamic changes in chromatin organization. Here, we review the molecular bases of chromatin alterations in response to DNA damage, focusing on core histone mobilization in mammalian cells. Building on our current view of nucleosome dynamics in response to DNA damage, we highlight open challenges and avenues for future development. In particular, we discuss the different levels of regulation of chromatin plasticity during the DNA damage response and their potential impact on cell function and epigenome maintenance.

Keywords: Chromatin dynamics; Chromatin remodelers; DNA damage repair; Epigenome maintenance; Histone chaperones; Histone variants.

Copyright © 2015 Elsevier B.V. All rights reserved.

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Figures

Fig.1

Fig.1. Histone dynamics in response to DNA damage: the issue of epigenome maintenance.

DNA damage (yellow star) elicits important chromatin rearrangements, including a loss of parental information (red) at the damage site due to the mobilization of pre-existing histones, and the incorporation of new information (green) with DNA damage-responsive PTMs, histone variant exchange and deposition of newly synthesized histones. The resulting pattern of histone variants and associated PTMs is likely to differ substantially from the original one. Future challenges in the field (open issues in blue) will be to determine to which extent the original information is diluted and whether or not the pre-existing chromatin landscape is ultimately faithfully restored after genotoxic stress, by parental histone recycling, histone variant exchange, active erasure of DNA damage-associated PTMs, and/or transmission of parental marks to newly deposited histones.

Fig.2

Fig.2. Cross-talks between histone dynamics in damaged chromatin and cellular functions.

The exchange of parental histones (red) with histones carrying new information (green) in response to DNA damage will impose - at least transient - changes in chromatin structure and function. Future work should closely examine to which extent these dynamics impact DNA metabolic activities (such as DNA repair and transcription) and cellular functions (proliferation and differentiation), and assess their consequences on cell identity. Conversely, it needs to be further explored how the initial chromatin organization, DNA damage type, cell cycle stage and cell state may regulate DNA damage-induced histone dynamics.

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