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.

RAD51/DMC1 细丝在单链 (ss)DNA 上的形成受到严格调控，这对于 DNA 双链断裂 (DSB) 修复中的同源搜索和链交换至关重要。FigNL1 AAA+++ ATPase 控制人类细胞中 RAD51 介导的重组。然而，它在配子发生中的作用仍未解决。在这里，我们表征了FIGNL1的种系特异性条件敲除（cKO）小鼠。Fignl1 cKO雄性小鼠表现出染色体突触缺陷和减数分裂DSB修复受损，RAD51/DMC1在减数分裂染色体上积累，支持FIGNL1在RAD51/DMC1丝组装后阶段的同源重组中的积极作用。Fignl1 cKO 精母细胞也在减数分裂前 S 期的染色体上积累 RAD51/DMC1。这些 RAD51/DMC1 组装体独立于减数分裂 DSB 的形成。我们还表明，纯化的FIGNL1 可以分解双链(ds)DNA 和ssDNA 上的RAD51 丝。这些结果表明，FIGNL1 在减数分裂前 S 期和减数分裂前期 I 期间限制 RAD51/DMC1 在天然 dsDNA 上的非生产性组装方面发挥了额外作用。