Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, MaRS Centre, West Tower, 661 University Avenue, Toronto, ON M5G 1M1, Canada.
Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, MaRS Centre, West Tower, 661 University Avenue, Toronto, ON M5G 1M1, Canada; Canada Research Chairs Program, Temerty Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Trends Genet. 2022 Mar;38(3):290-304. doi: 10.1016/j.tig.2021.08.016. Epub 2021 Sep 28.
The maintenance of genome stability and cellular homeostasis depends on the temporal and spatial coordination of successive events constituting the classical DNA damage response (DDR). Recent findings suggest close integration and coordination of DDR signaling with specific cellular processes. The mechanisms underlying such coordination remain unclear. We review emerging crosstalk between DNA repair factors, chromatin remodeling, replication, transcription, spatial genome organization, cytoskeletal forces, and liquid-liquid phase separation (LLPS) in mediating DNA repair. We present an overarching DNA repair framework within which these dynamic processes intersect in nuclear space over time. Collectively, this interplay ensures the efficient assembly of DNA repair proteins onto shifting genome structures to preserve genome stability and cell survival.
基因组稳定性和细胞内稳态的维持依赖于构成经典 DNA 损伤反应 (DDR) 的连续事件的时空协调。最近的发现表明，DDR 信号与特定的细胞过程密切整合和协调。这种协调的机制尚不清楚。我们综述了 DNA 修复因子、染色质重塑、复制、转录、空间基因组组织、细胞骨架力和液-液相分离 (LLPS) 之间新兴的串扰在介导 DNA 修复中的作用。我们提出了一个总体的 DNA 修复框架，在这个框架内，这些动态过程随着时间的推移在核空间中交汇。总的来说，这种相互作用确保了 DNA 修复蛋白有效地组装到不断变化的基因组结构上，以维持基因组稳定性和细胞存活。
