The relationship between histone posttranslational modification and DNA damage signaling and repair

Abstract

Purpose: The cellular response to DNA damage occurs in the context of an organized chromatin environment in order to maintain genome integrity. Immediately after DNA damage, an array of histone modifications are induced to relieve the physical constraints of the chromatin environment, mark the site as damaged, and function as a platform for the assembly of mediator and effector proteins of DNA damage response signaling pathway. Changes in chromatin structure in the vicinity of the DNA double-strand break (DSB) facilitates the efficient initiation of the DNA damage signaling cascade. Failure of induction of DNA damage responsive histone modifications may lead to genome instability and cancer. Here we will discuss our current understanding of the DNA damage responsive histone modifications and their role in DNA repair as well as their implications for genome stability. We further discuss recent studies which highlight not only how histone modification has involved in the signaling and remodeling at the DSB but also how it influences the DNA repair pathway choice.

Conclusions: Histone modifications pattern alter during the induction of DNA DSBs induction as well as during the repair and recovery phase of DNA damage response. It will be interesting to understand more precisely, how DSBs within chromatin are repaired by HR and NHEJ. The emergence of proteomic and genomic technologies in combination with advanced microscopy and imaging methods will help in better understanding the role of chromatin environment in the regulation of genome stability.

Keywords:

• Chromatin remodeling
• DNA damage
• DNA double-strand break
• genome stability
• histone modification

Acknowledgements

We thank members of the Hendzel lab for useful discussions and comments for the review. Michael Hendzel lab is supported by the Canadian Institutes of Health Research (CHIR).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Canadian Institute of Health Research [grant number MOP133430].

Notes on contributors

Ajit K Sharma

Ajit K Sharma is currently a post doctoral research fellow at Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta.

Michael J. Hendzel

Michael Hendzel is a professor of Department of Oncology and adjunct professor at Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta.