生物
Ku80型
非同源性末端接合
DNA
DNA修复
同源重组
二聚体
细胞生物学
生物物理学
遗传学
DNA结合蛋白
基因
转录因子
化学
有机化学
作者
Christopher J. Buehl,Noah J Goff,Steven W. Hardwick,Martin Gellert,Tom L. Blundell,Wei Yang,Amanda K. Chaplin,Katheryn Meek
出处
期刊:Molecular Cell
[Elsevier]
日期:2023-03-01
卷期号:83 (5): 698-714.e4
被引量:10
标识
DOI:10.1016/j.molcel.2023.01.012
摘要
Non-homologous end joining is the major double-strand break repair (DSBR) pathway in mammals. DNA-PK is the hub and organizer of multiple steps in non-homologous end joining (NHEJ). Recent high-resolution structures show how two distinct NHEJ complexes "synapse" two DNA ends. One complex includes a DNA-PK dimer mediated by XLF, whereas a distinct DNA-PK dimer forms via a domain-swap mechanism where the C terminus of Ku80 from one DNA-PK protomer interacts with another DNA-PK protomer in trans. Remarkably, the distance between the two synapsed DNA ends in both dimers is the same (∼115 Å), which matches the distance observed in the initial description of an NHEJ long-range synaptic complex. Here, a mutational strategy is used to demonstrate distinct cellular function(s) of the two dimers: one promoting fill-in end processing, while the other promotes DNA end resection. Thus, the specific DNA-PK dimer formed (which may be impacted by DNA end structure) dictates the mechanism by which ends will be made ligatable.
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