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RAD51 separation of function mutation disables replication fork maintenance but preserves DSB repair.


ABSTRACT: Homologous recombination (HR) protects replication forks (RFs) and repairs DNA double-strand breaks (DSBs). Within HR, BRCA2 regulates RAD51 via two interaction regions: the BRC repeats to form filaments on single-stranded DNA and exon 27 (Ex27) to stabilize the filament. Here, we identified a RAD51 S181P mutant that selectively disrupted the RAD51-Ex27 association while maintaining interaction with BRC repeat and proficiently forming filaments capable of DNA binding and strand invasion. Interestingly, RAD51 S181P was defective for RF protection/restart but proficient for DSB repair. Our data suggest that Ex27-mediated stabilization of RAD51 filaments is required for the protection of RFs, while it seems dispensable for the repair of DSBs.

SUBMITTER: Son MY 

PROVIDER: S-EPMC10993188 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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RAD51 separation of function mutation disables replication fork maintenance but preserves DSB repair.

Son Mi Young MY   Belan Ondrej O   Spirek Mario M   Cibulka Jakub J   Nikulenkov Fedor F   Kim You Young YY   Hwang Sunyoung S   Myung Kyungjae K   Montagna Cristina C   Kim Tae Moon TM   Krejci Lumir L   Hasty Paul P  

iScience 20240316 4


Homologous recombination (HR) protects replication forks (RFs) and repairs DNA double-strand breaks (DSBs). Within HR, BRCA2 regulates RAD51 via two interaction regions: the BRC repeats to form filaments on single-stranded DNA and exon 27 (Ex27) to stabilize the filament. Here, we identified a RAD51 S181P mutant that selectively disrupted the RAD51-Ex27 association while maintaining interaction with BRC repeat and proficiently forming filaments capable of DNA binding and strand invasion. Interes  ...[more]

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