Chromatin Response to DNA Double-Strand Break Damage

Abstract

Manipulation of chromatin, in which genomic DNA is packaged, is a fundamental requirement for all DNA-based metabolic processes in eukayotic cells. Histone variant incorporation, histone post-translational modifications, and ATP-dependent chromatin remodeling are three major strategies for chromatin manipulation, and are relatively well characterized in transcriptional regulation. Emerging lines of evidence indicate that histone variants (H2AX and H2A.Z), histone post-translational modifications (acetylation, phosphorylation, methylation and ubiquitination) and chromatin-remodeling complexes (INO80, SWR1, SWI/SNF, RSC and NuRD) are important and direct players in the DNA double-strand break (DSB) response as well. New studies also reveal that incorporation of histone variants into nucleosomes, histone modifications and ATP-dependent chromatin remodeling are specifically and intimately connected during the DSB damage response. This article summarizes the recent advances in our understanding of the relationship between chromatin modifications and the DSB damage response.

KEYWORDS::

• γ-H2AX
• acetylation
• ATP-dependent chromatin remodeling
• DNA damage
• DNA double-strand break
• DSB
• H2AX
• H2A.Z
• histone post-transcriptional modifications
• histone variant
• INO80
• methylation
• NuRD
• phosphorylation
• RSC
• SWI/SNF
• SWR1
• ubiquitination

Acknowledgements

The author wishes to apologize to colleagues whose relevant studies were not cited, owing to the focused scope of the article and space limitation, and is grateful to Mark Badeaux, Xuetong Shen, Mingming Chen and Aimee Iberg for their comments on this work.

Financial & competing interests disclosure

Funding for Yunhe Bao is provided by the Epigenetic Scholar Program in the MD Anderson Cancer Center, TX, USA. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Funding for Yunhe Bao is provided by the Epigenetic Scholar Program in the MD Anderson Cancer Center, TX, USA. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.