Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination

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 re...

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Main Authors: Kazumasa Takemoto, Naoki Tani, Yuki Takada-Horisawa, Sayoko Fujimura, Nobuhiro Tanno, Mariko Yamane, Kaho Okamura, Michihiko Sugimoto, Kimi Araki, Kei-ichiro Ishiguro
Format: Article
Language:English
Published: Elsevier 2020-05-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720306392
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author Kazumasa Takemoto
Naoki Tani
Yuki Takada-Horisawa
Sayoko Fujimura
Nobuhiro Tanno
Mariko Yamane
Kaho Okamura
Michihiko Sugimoto
Kimi Araki
Kei-ichiro Ishiguro
author_facet Kazumasa Takemoto
Naoki Tani
Yuki Takada-Horisawa
Sayoko Fujimura
Nobuhiro Tanno
Mariko Yamane
Kaho Okamura
Michihiko Sugimoto
Kimi Araki
Kei-ichiro Ishiguro
author_sort Kazumasa Takemoto
collection DOAJ
description 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.
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spelling doaj.art-0d8530f0fc044b2790b7d99713c751232022-12-22T01:24:19ZengElsevierCell Reports2211-12472020-05-01318Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic RecombinationKazumasa Takemoto0Naoki Tani1Yuki Takada-Horisawa2Sayoko Fujimura3Nobuhiro Tanno4Mariko Yamane5Kaho Okamura6Michihiko Sugimoto7Kimi Araki8Kei-ichiro Ishiguro9Department 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, JapanLiaison Laboratory Research Promotion Center, IMEG, Kumamoto University, Kumamoto 860-0811, JapanDepartment of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto 860-0811, JapanLiaison Laboratory Research Promotion Center, IMEG, Kumamoto University, Kumamoto 860-0811, JapanDepartment of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto 860-0811, JapanRIKEN, Center for Biosystems Dynamics Research, Kobe 650-0047, JapanDepartment of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto 860-0811, JapanInstitute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, JapanInstitute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan; Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto 860-0811, JapanDepartment of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto 860-0811, Japan; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720306392Meiosismeiotic recombinationRAD51DSBspermatogenesisChromosome
spellingShingle Kazumasa Takemoto
Naoki Tani
Yuki Takada-Horisawa
Sayoko Fujimura
Nobuhiro Tanno
Mariko Yamane
Kaho Okamura
Michihiko Sugimoto
Kimi Araki
Kei-ichiro Ishiguro
Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination
Cell Reports
Meiosis
meiotic recombination
RAD51
DSB
spermatogenesis
Chromosome
title Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination
title_full Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination
title_fullStr Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination
title_full_unstemmed Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination
title_short Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination
title_sort meiosis specific c19orf57 4930432k21rik brme1 modulates localization of rad51 and dmc1 to dsbs in mouse meiotic recombination
topic Meiosis
meiotic recombination
RAD51
DSB
spermatogenesis
Chromosome
url http://www.sciencedirect.com/science/article/pii/S2211124720306392
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