Blurring the line between the DNA damage response and transcription: the importance of chromatin dynamics - PubMed (original) (raw)

Review

Blurring the line between the DNA damage response and transcription: the importance of chromatin dynamics

Salomé Adam et al. Exp Cell Res. 2014.

Abstract

DNA damage interferes with the progression of transcription machineries. A tight coordination of transcription with signaling and repair of DNA damage is thus critical for safeguarding genome function. This coordination involves modulations of chromatin organization. Here, we focus on the central role of chromatin dynamics, in conjunction with DNA Damage Response (DDR) factors, in controlling transcription inhibition and restart at sites of DNA damage in mammalian cells. Recent work has identified chromatin modifiers and histone chaperones as key regulators of transcriptional activity in damaged chromatin regions. Conversely, the transcriptional state of chromatin before DNA damage influences both DNA damage signaling and repair. We discuss the importance of chromatin plasticity in coordinating the interplay between the DDR and transcription, with major implications for cell fate maintenance.

Keywords: Chromatin modifications; DNA damage; Genome integrity; Histone dynamics; Transcription coupled repair; Transcription regulation.

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Figures

Figure 1. Importance of chromatin dynamics in the transcriptional regulation of damaged genes

Chromatin modifiers (orange) and histone chaperones (blue, purple) involved in regulating transcription inhibition (top) and recovery (bottom) in damaged chromatin regions in response to DSBs, UV lesions, oxidative damage (DNA damage is represented by a star). DNA-damage-responsive chromatin modifications associated with active transcription (green) and silencing (red) are represented. ac : acetylation ; me : methylation ; ub : ubiquitylation. Given that RNF8/168 ubiquitin ligases are not known to target K118/119 residues on H2A, an intermediate factor is likely involved as indicated by a question mark.

Figure 2. Histone dynamics at the core of the interplay between the DDR and transcription

DNA damage-induced histone dynamics, including histone exchange and post-translational modifications, govern local changes in chromatin transcriptional activity. Conversely, chromatin transcriptional state, via histone modifications, modulates DNA damage signaling and repair.

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Blurring the line between the DNA damage response and transcription: the importance of chromatin dynamics - PubMed (original) (raw)