FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination
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 rem...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-10-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42576-w |
| _version_ | 1797647296127565824 |
|---|---|
| author | Masaru Ito Asako Furukohri Kenichiro Matsuzaki Yurika Fujita Atsushi Toyoda Akira Shinohara |
| author_facet | Masaru Ito Asako Furukohri Kenichiro Matsuzaki Yurika Fujita Atsushi Toyoda Akira Shinohara |
| author_sort | Masaru Ito |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T15:14:16Z |
| format | Article |
| id | doaj.art-e1790d02b8df41b7822952d6cc753b45 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T15:14:16Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-e1790d02b8df41b7822952d6cc753b452023-10-29T12:29:58ZengNature PortfolioNature Communications2041-17232023-10-0114111910.1038/s41467-023-42576-wFIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombinationMasaru Ito0Asako Furukohri1Kenichiro Matsuzaki2Yurika Fujita3Atsushi Toyoda4Akira Shinohara5Institute for Protein Research, Osaka University, SuitaInstitute for Protein Research, Osaka University, SuitaInstitute for Protein Research, Osaka University, SuitaInstitute for Protein Research, Osaka University, SuitaAdvanced Genomics Center, National Institute of Genetics, MishimaInstitute for Protein Research, Osaka University, SuitaAbstract 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.https://doi.org/10.1038/s41467-023-42576-w |
| spellingShingle | Masaru Ito Asako Furukohri Kenichiro Matsuzaki Yurika Fujita Atsushi Toyoda Akira Shinohara FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination Nature Communications |
| title | FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination |
| title_full | FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination |
| title_fullStr | FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination |
| title_full_unstemmed | FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination |
| title_short | FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination |
| title_sort | fignl1 aaa atpase remodels rad51 and dmc1 filaments in pre meiotic dna replication and meiotic recombination |
| url | https://doi.org/10.1038/s41467-023-42576-w |
| work_keys_str_mv | AT masaruito fignl1aaaatpaseremodelsrad51anddmc1filamentsinpremeioticdnareplicationandmeioticrecombination AT asakofurukohri fignl1aaaatpaseremodelsrad51anddmc1filamentsinpremeioticdnareplicationandmeioticrecombination AT kenichiromatsuzaki fignl1aaaatpaseremodelsrad51anddmc1filamentsinpremeioticdnareplicationandmeioticrecombination AT yurikafujita fignl1aaaatpaseremodelsrad51anddmc1filamentsinpremeioticdnareplicationandmeioticrecombination AT atsushitoyoda fignl1aaaatpaseremodelsrad51anddmc1filamentsinpremeioticdnareplicationandmeioticrecombination AT akirashinohara fignl1aaaatpaseremodelsrad51anddmc1filamentsinpremeioticdnareplicationandmeioticrecombination |