The role of histone H3K36me3 writers, readers and erasers in maintaining genome stability

Abstract

Histone Post-Translational Modifications (PTMs) play fundamental roles in mediating DNA-related processes such as transcription, replication and repair. The histone mark H3K36me3 and its associated methyltransferase SETD2 (Set2 in yeast) are archetypical in this regard, performing critical roles in each of these DNA transactions. Here, we present an overview of H3K36me3 regulation and the roles of its writers, readers and erasers in maintaining genome stability through facilitating DNA double-strand break (DSB) repair, checkpoint signalling and replication stress responses. Further, we consider how loss of SETD2 and H3K36me3, frequently observed in a number of different cancer types, can be specifically targeted in the clinic through exploiting loss of particular genome stability functions.

Keywords: Cancer; DNA integrity checkpoint; DNA repair; Genome stability; H3K36me3; Replication stress; SETD2; Transcription regulation.