title: The repair and signaling responses to DNA double-strand breaks.
abstract: A DNA double-strand break (DSB) has long been recognized as a severe cellular lesion, potentially representing an initiating event for carcinogenesis or cell death. The evolution of DSB repair pathways as well as additional processes, such as cell cycle checkpoint arrest, to minimize the cellular impact of DSB formation was, therefore, not surprising. However, the depth and complexity of the DNA damage responses being revealed by current studies were unexpected. Perhaps the most surprising finding to emerge is the dramatic changes to chromatin architecture that arise in the DSB vicinity. In this review, we overview the cellular response to DSBs focusing on DNA repair pathways and the interface between them. We consider additional events which impact upon these DSB repair pathways, including regulated arrest of cell cycle progression and chromatin architecture alterations. Finally, we discuss the impact of defects in these processes to human disease.
authors.affiliation: Department of Biochemistry & Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Goodarzi
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Jeggo
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004260:DNA Repair; D004194:Disease / Q000235:genetics; D006801:Humans; D011995:Recombination, Genetic; D059767:Recombinational DNA Repair; D015398:Signal Transduction