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

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 promoted by various RAD51-interacting proteins including RAD51 paralogues. 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, which binds to RAD51 as well as SWSAP1. Purified FIGNL1 promotes the dissociation of RAD51 from ssDNAs. The dismantling activity of FIGNL1 does not require its ATPase but depends on RAD51-binding. 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.
Mesh Terms:
ATPases Associated with Diverse Cellular Activities, Amino Acid Motifs, Amino Acid Sequence, Animals, Cell Line, Chromosomes, Human, DNA, DNA Damage, DNA-Binding Proteins, Germ Cells, Humans, Mice, Inbred C57BL, Mice, Knockout, Microtubule-Associated Proteins, Mitosis, Models, Biological, Nuclear Proteins, Protein Binding, Rad51 Recombinase, Rec A Recombinases, Sequence Homology, Amino Acid
Nat Commun
Date: Dec. 29, 2018
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