University of Southern California, Molecular and Computational Biology Department, Los Angeles, CA 90089, USA.
University of Southern California, Molecular and Computational Biology Department, Los Angeles, CA 90089, USA.
Curr Opin Genet Dev. 2021 Dec;71:206-215. doi: 10.1016/j.gde.2021.09.007. Epub 2021 Oct 28.
Studies across different organisms show that nuclear architecture and dynamics play central roles in different aspects of homologous recombination (HR) repair. Here we review the most recent discoveries in this field, ranging from directed motions mediating relocalization pathways, to global chromatin mobilization, local DNA looping, and changes in repair focus properties associated with clustering and phase separation. We discuss how these dynamics work in different contexts, including molecular mechanisms and regulatory pathways involved. We specifically highlight how they function in pericentromeric heterochromatin, which presents a unique environment for HR repair given the abundance of repeated DNA sequences prone to aberrant recombination, the 'silent' chromatin state, and the phase separation characterizing this domain.
不同生物的研究表明，核结构和动力学在同源重组 (HR) 修复的不同方面起着核心作用。在这里，我们回顾了该领域的最新发现，范围从介导重定位途径的定向运动，到全局染色质动员、局部 DNA 环化以及与聚类和相分离相关的修复焦点特性的变化。我们讨论了这些动力学在不同环境中的工作方式，包括涉及的分子机制和调节途径。我们特别强调了它们在着丝粒异染色质中的功能，鉴于富含易于发生异常重组的重复 DNA 序列、“沉默”染色质状态以及表征该区域的相分离，着丝粒异染色质为 HR 修复提供了独特的环境。
