重组DNA修复过程中置换环的动态处理
Dynamic Processing of Displacement Loops during Recombinational DNA Repair.
作者信息
Piazza Aurèle, Shah Shanaya Shital, Wright William Douglass, Gore Steven K, Koszul Romain, Heyer Wolf-Dietrich
机构信息
Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA 95616, USA; Groupe Régulation spatiale des génomes, Department of Genomes and Genetics, Institut Pasteur, CNRS UMR 3525, 75015 Paris, France.
Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA 95616, USA.
出版信息
Mol Cell. 2019 Mar 21;73(6):1255-1266.e4. doi: 10.1016/j.molcel.2019.01.005. Epub 2019 Feb 5.
Displacement loops (D-loops) are pivotal intermediates of homologous recombination (HR), a universal DNA double strand break (DSB) repair pathway. We developed a versatile assay for the physical detection of D-loops in vivo, which enabled studying the kinetics of their formation and defining the activities controlling their metabolism. Nascent D-loops are detected within 2 h of DSB formation and extended in a delayed fashion in a genetic system designed to preclude downstream repair steps. The majority of nascent D-loops are disrupted by two pathways: one supported by the Srs2 helicase and the other by the Mph1 helicase and the Sgs1-Top3-Rmi1 helicase-topoisomerase complex. Both pathways operate without significant overlap and are delineated by the Rad54 paralog Rdh54 in an ATPase-independent fashion. This study uncovers a layer of quality control of HR relying on nascent D-loop dynamics.
置换环（D环）是同源重组（HR）的关键中间体，同源重组是一种普遍的DNA双链断裂（DSB）修复途径。我们开发了一种通用的检测方法，用于在体内物理检测D环，这使得研究它们形成的动力学并确定控制其代谢的活性成为可能。在DSB形成后2小时内即可检测到新生D环，并在一个旨在排除下游修复步骤的遗传系统中以延迟的方式进行延伸。大多数新生D环通过两条途径被破坏：一条由Srs2解旋酶支持，另一条由Mph1解旋酶和Sgs1-Top3-Rmi1解旋酶-拓扑异构酶复合体支持。这两条途径的运作没有明显重叠，并且由Rad54旁系同源物Rdh54以一种不依赖ATP酶的方式进行区分。这项研究揭示了一层依赖于新生D环动力学的同源重组质量控制机制。
Zotero 插件