Chromatin modifiers and remodellers in DNA repair and signalling.

Abstract

Following the seminal unravelling of the double helical structure of DNA by Watson, Crick and colleagues in 1952, work of equal significance and similarly recognized by a Nobel Prize led to the appreciation that DNA is an unstable structure subject to damage from chemical attack by agents arising endogenously or exogenously, and from metabolic transactions, such as replication and transcription [1,2]. The past 50 years has seen mounting recognition of the enormous significance of DNA damage response (DDR) pathways in protecting against the harmful effects of this damage, and particularly our understanding of the DNA repair processes [1]. Indeed, we now understand the importance these pathways play in cancer avoidance, in protection against ageing and in ensuring normal development [3,4]. We now have a good understanding of the basic DNA repair processes, at least when considering their action on naked DNA. However, in a cellular setting, our DNA is organized within a chromatin environment, which can represent a diverse range from open to closed conformations of distinct types. Our DNA sequences can be unique or repetitive. And there are ongoing DNA transactions, which can profoundly influence the DNA repair processes. Thus, a current focus of research is to understand how chromatin is modified and reorganized to allow optimal DNA repair and interplay between the DDR and metabolic processes such as transcription and replication. Our goal in this themed issue is to review our current understanding of the epigenetic changes that arise in the vicinity of DNA double strand breaks (DSBs) and the chromatin remodelling complexes employed to reorganize chromatin. While the focus lies on DSBs, we include a consideration of how DNA damage influences transcription/replication as well as how chromatin is remodelled to allow replication since an evaluation of these …