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bioRxiv · 10.1101/2023.03.26.534288

FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in meiotic DNA replication and recombination

Ito, M.·Furukohri, A.·Matsuzaki, K.·Fujita, Y.·Toyoda, A.·Shinohara, A.
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Abstract

The formation of RAD51/DMC1 filaments on single-stranded (ss)DNAs essential for homology search and strand exchange in DNA double-strand break (DSB) repair is tightly regulated. FIGNL1 AAA+++ ATPase controls RAD51-mediated recombination in human cells. However, its role in gametogenesis remains unsolved. Here, we characterized a germ-line-specific conditional knockout (cKO) mouse of FIGNL1. Fignl1 cKO male mice showed defective chromosome synapsis and impaired meiotic DSB repair with the accumulation of RAD51/DMC1 on meiotic chromosomes, supporting a positive role of FIGNL1 in homologous recombination at a post-assembly stage of RAD51/DMC1 filaments. Fignl1 cKO spermatocytes also accumulate RAD51/DMC1 on chromosomes in pre-meiotic S-phase. These RAD51/DMC1 assemblies are independent of meiotic DSB formation. We also showed that purified FIGNL1 dismantles RAD51 filament on double-stranded (ds)DNA as well as ssDNA. These results suggest an additional role of FIGNL1 in limiting the non-productive assembly of RAD51/DMC1 on native dsDNAs during pre-meiotic S-phase and meiotic prophase I.

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Ito, M., Furukohri, A., Matsuzaki, K., Fujita, Y., Toyoda, A., Shinohara, A.. 2023-03-26. FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in meiotic DNA replication and recombination. https://doi.org/10.1101/2023.03.26.534288

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