A RAD51–ADP double filament structure unveils the mechanism of filament dynamics in homologous recombination

Author:

Luo Shih-ChiORCID,Yeh Min-Chi,Lien Yu-Hsiang,Yeh Hsin-Yi,Siao Huei-Lun,Tu I-PingORCID,Chi PeterORCID,Ho Meng-ChiaoORCID

Abstract

AbstractATP-dependent RAD51 recombinases play an essential role in eukaryotic homologous recombination by catalyzing a four-step process: 1) formation of a RAD51 single-filament assembly on ssDNA in the presence of ATP, 2) complementary DNA strand-exchange, 3) ATP hydrolysis transforming the RAD51 filament into an ADP-bound disassembly-competent state, and 4) RAD51 disassembly to provide access for DNA repairing enzymes. Of these steps, filament dynamics between the ATP- and ADP-bound states, and the RAD51 disassembly mechanism, are poorly understood due to the lack of near-atomic-resolution information of the ADP-bound RAD51–DNA filament structure. We report the cryo-EM structure of ADP-bound RAD51–DNA filaments at 3.1 Å resolution, revealing a unique RAD51 double-filament that wraps around ssDNA. Structural analysis, supported by ATP-chase and time-resolved cryo-EM experiments, reveals a collapsing mechanism involving two four-protomer movements along ssDNA for mechanical transition between RAD51 single- and double-filament without RAD51 dissociation. This mechanism enables elastic change of RAD51 filament length during structural transitions between ATP- and ADP-states.

Funder

Academia Sinica

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Structure-based approaches in synthetic lethality strategies;Current Opinion in Structural Biology;2024-10

2. Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer;Frontiers in Oncology;2024-08-02

3. Structure of RADX and mechanism for regulation of RAD51 nucleofilaments;Proceedings of the National Academy of Sciences;2024-03-11

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