Spatial Regulation of Genomes, Institut Pasteur, CNRS, UMR3525, 28 Rue du Docteur Roux, 75015, Paris, France.
Department of Microbiology and Molecular Genetics, University of California, Davis, One Shields Ave, Davis, CA, 95616, USA.
Curr Genet. 2019 Dec;65(6):1333-1340. doi: 10.1007/s00294-019-00995-7. Epub 2019 May 23.
DNA double-strand breaks are genotoxic lesions whose repair can be templated off an intact DNA duplex through the conserved homologous recombination (HR) pathway. Because it mainly consists of a succession of non-covalent associations of molecules, HR is intrinsically reversible. Reversibility serves as an integral property of HR, exploited and tuned at various stages throughout the pathway with anti- and pro-recombinogenic consequences. Here, we focus on the reversibility of displacement loops (D-loops), a central DNA joint molecule intermediate whose dynamics and regulation have recently been physically probed in somatic S. cerevisiae cells. From homology search to repair completion, we discuss putative roles of D-loop reversibility in repair fidelity and outcome.
DNA 双链断裂是遗传毒性损伤,其修复可以通过保守的同源重组 (HR) 途径在完整的 DNA 双链模板上进行。由于 HR 主要由分子的一系列非共价结合组成,因此它本质上是可逆的。可逆性是 HR 的一个固有特性,在整个途径的各个阶段都被利用和调整,具有抗重组和促进重组的后果。在这里,我们关注的是置换环 (D-loops) 的可逆性,D-loops 是一种中央 DNA 连接分子中间体,其动力学和调节最近在体细胞酿酒酵母细胞中得到了物理探测。从同源搜索到修复完成,我们讨论了 D-loop 可逆性在修复保真度和结果中的可能作用。