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

Mi Young Son·Ondrej Belan·Mario Spirek·Jakub Cibulka·Fedor Nikulenkov·You Young Kim·Sunyoung Hwang·Kyungjae Myung·Cristina Montagna·Tae Moon Kim·Lumir Krejci·Paul Hasty
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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.

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Mi Young Son, Ondrej Belan, Mario Spirek, Jakub Cibulka, Fedor Nikulenkov, You Young Kim, Sunyoung Hwang, Kyungjae Myung, Cristina Montagna, Tae Moon Kim, Lumir Krejci, Paul Hasty. 2024-03-16. RAD51 separation of function mutation disables replication fork maintenance but preserves DSB repair.. https://doi.org/10.1016/j.isci.2024.109524

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