Puc Janusz, Aggarwal Aneel K, Rosenfeld Michael G
EMD Serono Research and Development Institute, Billerica, Massachusetts 01821, USA; he was previously at the Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093-0648, USA.
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Nat Rev Mol Cell Biol. 2017 Aug;18(8):471-476. doi: 10.1038/nrm.2017.43. Epub 2017 May 24.
The idea that signal-dependent transcription might involve the generation of transient DNA nicks or even breaks in the regulatory regions of genes, accompanied by activation of DNA damage repair pathways, would seem to be counterintuitive, as DNA damage is usually considered harmful to cellular integrity. However, recent studies have generated a substantial body of evidence that now argues that programmed DNA single- or double-strand breaks can, at least in specific cases, have a role in transcription regulation. Here, we discuss the emerging functions of DNA breaks in the relief of DNA torsional stress and in promoter and enhancer activation.
信号依赖型转录可能涉及在基因调控区域产生瞬时DNA切口甚至断裂,并伴随DNA损伤修复途径的激活,这一观点似乎有违直觉,因为DNA损伤通常被认为对细胞完整性有害。然而,最近的研究已产生了大量证据,表明程序性DNA单链或双链断裂至少在特定情况下可参与转录调控。在此,我们讨论DNA断裂在缓解DNA扭转应力以及启动子和增强子激活方面新出现的功能。