Biology subjects

Furukohri, A.

Publications and source records attributed to Furukohri, A..

3 recordsLinked to original sources

bioRxiv2026

Age-dependent accumulation of RAD51 on non-damaged chromosomes prevents chromosome segregation in mammalian oocytes

RAD51 is targeted to single-stranded (ss)DNA for homologous recombination and DNA replication fork homeostasis. However, the physiological consequences of RAD51 binding to intact double-stranded (ds)DNA, which is tightly limited in vivo, remain elusive. Here we revealed an intrinsic property of RAD51 to bind chromosome axes where cohesin and condensin bind, which is actively suppressed by FIGNL1 AAA+ ATPase. In Fignl1-deficient mouse oocytes, an age-dependent RAD51 accumulation with little DNA damage leads to improper chromosomal localization of condensin II and topoisomerase II, failure in chromosome condensation with massive chromosome entanglement, and meiosis I arrest. We propose that promiscuous RAD51 binding to non-damaged chromosomes, which is prevented by a RAD51 remodeler, is a unique type of chromosomal pathology associated with genome instability.

cell biology↗

bioRxiv2024

Post-translational cleavage of Mei5 of Dmc1 mediator, Mei5-Sae3 complex, in yeast meiosis

Interhomolog recombination in meiosis is mediated by the Dmc1 recombinase. The Mei5-Sae3 complex of S. cerevisiae promotes Dmc1 assembly and functions with Dmc1 for homology-mediated repair of meiotic DNA double-strand breaks. How Mei5-Sae3 facilitates Dmc1 assembly remains poorly understood. In this study, we created and characterized several mei5 mutants featuring the amino acid substitutions of basic residues. We found that Arg97 of Mei5, conserved in its ortholog, SFR1(complex with SWI5), RAD51 mediator, in humans and other organisms, is critical for complex formation with Sae3 for Dmc1 assembly. Moreover, the substitution of Arg117 with Ala in Mei5 resulted in the production of a C-terminal truncated Mei5 protein during yeast meiosis. Notably, the shorter Mei5-R117A protein was observed in meiotic cells but not in mitotic cells when expressed, suggesting a unique regulation of Dmc1-mediated recombination by post-translational processing of Mei5-Sae3.

molecular biology↗

bioRxiv2023

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

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.

molecular biology↗