Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin

IF 45.8 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2024-12-05 DOI:10.1126/science.adr7920
Alexander Carver, Tai-Yuan Yu, Luke A. Yates, Travis White, Raymond Wang, Katie Lister, Maria Jasin, Xiaodong Zhang
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引用次数: 0

Abstract

Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central component of several crucial processes in repairing DNA and protecting genome integrity, forms filaments on DNA, which are tightly regulated. One of these RAD51 regulators is FIGNL1 (fidgetin-like 1), which prevents RAD51 genotoxic chromatin association in normal cells and persistent RAD51 foci upon DNA damage. The cryogenic electron microscopy–imaged structure of FIGNL1 in complex with RAD51 reveals that FIGNL1 forms a nonplanar hexamer and encloses RAD51 N terminus in the FIGNL1 hexamer pore. Mutations in pore loop or catalytic residues of FIGNL1 render it defective in filament disassembly and are lethal in mouse embryonic stem cells. Our study reveals a distinct mechanism for removing RAD51 from bound substrates and provides the molecular basis for FIGNL1 in maintaining genome stability.
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FIGNL1解离RAD51与DNA和染色质的分子基础
维持基因组的完整性是一个必要且具有挑战性的过程。RAD51重组酶在修复DNA和保护基因组完整性的几个关键过程中起着核心作用,它在DNA上形成细丝,并受到严格调控。其中一种RAD51调节因子是FIGNL1,它可以在细胞中DNA损伤和基因毒性染色质关联的情况下或之后阻止持续的RAD51病灶。FIGNL1与RAD51复合物的低温电镜结构显示,FIGNL1形成非平面六聚体,并且在FIGNL1六聚体孔中有RAD51 N端包膜。FIGNL1的孔环或催化残基的突变使其在细丝拆卸中存在缺陷,并且在小鼠胚胎干细胞中是致命的。我们的研究揭示了从结合底物中去除RAD51的独特机制,并为FIGNL1维持基因组稳定性提供了分子基础。
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来源期刊
Science
Science 综合性期刊-综合性期刊
CiteScore
61.10
自引率
0.90%
发文量
0
审稿时长
2.1 months
期刊介绍: Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research. Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated. Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.
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