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Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases

Guangxue Liu, Jimin Li, Boxue He, Jiaqi Yan, Jingyu Zhao, Xuejie Wang, Xiaocong Zhao, Jingyan Xu, Yeyao Wu, Simin Zhang, Xiaoli Gan, Chun Zhou, Xiangpan Li, Xinghua Zhang and Xuefeng Chen ()
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Guangxue Liu: Renmin Hospital of Wuhan University, Wuhan University
Jimin Li: Renmin Hospital of Wuhan University, Wuhan University
Boxue He: University of Texas Health Science Center
Jiaqi Yan: Renmin Hospital of Wuhan University, Wuhan University
Jingyu Zhao: Renmin Hospital of Wuhan University, Wuhan University
Xuejie Wang: Renmin Hospital of Wuhan University, Wuhan University
Xiaocong Zhao: Wuhan University
Jingyan Xu: Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
Yeyao Wu: Zhejiang University School of Medicine
Simin Zhang: Renmin Hospital of Wuhan University, Wuhan University
Xiaoli Gan: Renmin Hospital of Wuhan University, Wuhan University
Chun Zhou: Zhejiang University School of Medicine
Xiangpan Li: Renmin Hospital of Wuhan University, Wuhan University
Xinghua Zhang: Renmin Hospital of Wuhan University, Wuhan University
Xuefeng Chen: Renmin Hospital of Wuhan University, Wuhan University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Central to homologous recombination (HR) is the assembly of Rad51 recombinase on single-strand DNA (ssDNA), forming the Rad51-ssDNA filament. How the Rad51 filament is efficiently established and sustained remains partially understood. Here, we find that the yeast ubiquitin ligase Bre1 and its human homolog RNF20, a tumor suppressor, function as recombination mediators, promoting Rad51 filament formation and subsequent reactions via multiple mechanisms independent of their ligase activities. We show that Bre1/RNF20 interacts with Rad51, directs Rad51 to ssDNA, and facilitates Rad51-ssDNA filament assembly and strand exchange in vitro. In parallel, Bre1/RNF20 interacts with the Srs2 or FBH1 helicase to counteract their disrupting effect on the Rad51 filament. We demonstrate that the above functions of Bre1/RNF20 contribute to HR repair in cells in a manner additive to the mediator protein Rad52 in yeast or BRCA2 in human. Thus, Bre1/RNF20 provides an additional layer of mechanism to directly control Rad51 filament dynamics.

Date: 2023
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DOI: 10.1038/s41467-023-38617-z

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