Histone methylation and the DNA damage response.

Mutation Research. Reviews in Mutation Research
Fade Gong, Kyle M Miller

Abstract

Preserving genome function and stability are paramount for ensuring cellular homeostasis, an imbalance in which can promote diseases including cancer. In the presence of DNA lesions, cells activate pathways referred to as the DNA damage response (DDR). As nuclear DNA is bound by histone proteins and organized into chromatin in eukaryotes, DDR pathways have evolved to sense, signal and repair DNA damage within the chromatin environment. Histone proteins, which constitute the building blocks of chromatin, are highly modified by post-translational modifications (PTMs) that regulate chromatin structure and function. An essential histone PTM involved in the DDR is histone methylation, which is regulated by histone methyltransferase (HMT) and histone demethylase (HDM) enzymes that add and remove methyl groups on lysine and arginine residues within proteins respectively. Methylated histones can alter how proteins interact with chromatin, including their ability to be bound by reader proteins that recognize these PTMs. Here, we review histone methylation in the context of the DDR, focusing on DNA double-strand breaks (DSBs), a particularly toxic lesion that can trigger genome instability and cell death. We provide a comprehensive overv...Continue Reading

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