Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination
Kazumasa Takemoto,
Naoki Tani,
Yuki Takada-Horisawa,
Sayoko Fujimura,
Nobuhiro Tanno,
Mariko Yamane,
Kaho Okamura,
Michihiko Sugimoto,
Kimi Araki,
Kei-ichiro Ishiguro
Affiliations
Kazumasa Takemoto
Department of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto 860-0811, Japan; Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan
Naoki Tani
Liaison Laboratory Research Promotion Center, IMEG, Kumamoto University, Kumamoto 860-0811, Japan
Yuki Takada-Horisawa
Department of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto 860-0811, Japan
Sayoko Fujimura
Liaison Laboratory Research Promotion Center, IMEG, Kumamoto University, Kumamoto 860-0811, Japan
Nobuhiro Tanno
Department of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto 860-0811, Japan
Mariko Yamane
RIKEN, Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
Kaho Okamura
Department of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto 860-0811, Japan
Michihiko Sugimoto
Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan
Kimi Araki
Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan; Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto 860-0811, Japan
Kei-ichiro Ishiguro
Department of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto 860-0811, Japan; Corresponding author
Summary: Meiotic recombination is critical for genetic exchange and generation of chiasmata that ensures faithful chromosome segregation during meiosis I. Meiotic recombination is initiated by DNA double-strand break (DSB) followed by multiple processes of DNA repair. The exact mechanisms for how recombinases localize to DSB remain elusive. Here, we show that C19orf57/4930432K21Rik/BRME1 is a player for meiotic recombination in mice. C19orf57/4930432K21Rik/BRME1 associates with single-stranded DNA (ssDNA) binding proteins, BRCA2 and MEILB2/HSF2BP, which are critical recruiters of recombinases onto DSB sites. Disruption of C19orf57/4930432K21Rik/BRME1 shows severe impact on DSB repair and male fertility. Remarkably, removal of ssDNA binding proteins from DSB sites is delayed, and reciprocally, the loading of RAD51 and DMC1 onto resected ssDNA is impaired in Brme1 knockout (KO) spermatocytes. We propose that C19orf57/4930432K21Rik/BRME1 modulates localization of recombinases to meiotic DSB sites through the interaction with the BRCA2-MEILB2/HSF2BP complex during meiotic recombination.
