ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses

• Published in: Philosophical transactions of the Royal Society of London. Series B. Biological sciences Vol. 372; no. 1731; p. 20160283
• Main Authors: Berger, N. Daniel, Stanley, Fintan K. T., Moore, Shaun, Goodarzi, Aaron A.
• Format: Journal Article
• Language: English
• Published: England The Royal Society 05.10.2017; The Royal Society Publishing
• Subjects: Animals; Ataxia; Ataxia telangiectasia; Ataxia telangiectasia mutated protein; Ataxia Telangiectasia Mutated Proteins - metabolism; Ataxia-Telangiectasia Mutated; Brain; Central nervous system; Chromatin; Chromatin - metabolism; Chromatin Assembly and Disassembly; Chromatin remodeling; Chromosomes; Commands; Damage; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded; DNA Damage; DNA repair; Double-strand break repair; Environmental impact; Epigenesis, Genetic; Genetic recombination; Humans; Kinases; Mice; Neurodegeneration; Oxidative Stress; Protein kinase; Protein-serine/threonine kinase; Rats; Repair; Review; Signal transduction; Signaling; neurodegeneration; ataxia-telangiectasia mutated; brain; chromatin; DNA damage; oxidative stress
• ISSN: 0962-8436; 1471-2970
• DOI: 10.1098/rstb.2016.0283

Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system. This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.