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bioRxiv · 10.1101/507632

Human RAD51 paralogue, SWSAP1, fosters RAD51 filament by regulating the anti-recombinase, FIGNL1 AAA+ ATPase

Matsuzaki, K.·Kondo, S.·Ishikawa, T.·Shinohara, A.
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Abstract

RAD51 assembly on single-stranded (ss)DNAs is a crucial step in the homology-dependent repair of DNA damage for genomic stability. The formation of the RAD51 filament is tightly regulated by various RAD51-interacting proteins. The familial breast cancer gene, BRCA2, as well as RAD52 and six RAD51 paralogues (SWSAP1, RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) promote RAD51 assembly on ssDNAs in humans. However, the mechanisms underlying the differential control of RAD51 filament dynamics by these factors remain largely unknown. Here, we report a role for the human RAD51 paralogue, SWSAP1, as a novel regulator of RAD51 assembly. Swsap1-deficient cells show defects in DNA damage-induced RAD51 assembly during both mitosis and meiosis. Defective RAD51 assembly in SWSAP1-depleted cells is suppressed by the depletion of FIGNL1, an AAA+ ATPase, which binds to RAD51 as well as SWSAP1. Purified FIGNL1 promotes the dissociation of RAD51 from ssDNAs. The in vitro dismantling activity of FIGNL1 does not require its ATPase but depends on RAD51-binding, suggesting a novel mechanism of RAD51 filament remodelling. Purified SWSAP1 inhibits the RAD51-dismantling activity of FIGNL1. Taken together, our data suggest that SWSAP1 protects RAD51 filaments by antagonizing the anti-recombinase, FIGNL1.

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Matsuzaki, K., Kondo, S., Ishikawa, T., Shinohara, A.. 2018-12-30. Human RAD51 paralogue, SWSAP1, fosters RAD51 filament by regulating the anti-recombinase, FIGNL1 AAA+ ATPase. https://doi.org/10.1101/507632

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