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NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis.
Zhang, Bin; Tang, Zhenghui; Li, Lejun; Lu, Lin-Yu.
Afiliación
  • Zhang B; Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Tang Z; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • Li L; Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Lu LY; Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cell Death Differ ; 27(7): 2176-2190, 2020 07.
Article en En | MEDLINE | ID: mdl-31965061
DNA double-strand breaks (DSBs) pose a serious threat to genomic stability. Paradoxically, hundreds of programed DSBs are generated by SPO11 in meiotic prophase, which are exclusively repaired by homologous recombination (HR) to promote obligate crossover between homologous chromosomes. In somatic cells, MRE11-RAD50-NBS1 (MRN) complex-dependent DNA end resection is a prerequisite for HR repair, especially for DSBs that are covalently linked with proteins or chemicals. Interestingly, all meiotic DSBs are linked with SPO11 after being generated. Although MRN complex's function in meiotic DSB repair has been established in lower organisms, the role of MRN complex in mammalian meiotic DSB repair is not clear. Here, we show that MRN complex is essential for repairing meiotic SPO11-linked DSBs in male mice. In male germ cells, conditional inactivation of NBS1, a key component of MRN complex, causes dramatic reduction of DNA end resection and defective HR repair in meiotic prophase. NBS1 loss severely disrupts chromosome synapsis, generates abnormal chromosome structures, and eventually leads to meiotic arrest and male infertility in mice. Unlike in somatic cells, the recruitment of NBS1 to SPO11-linked DSB sites is MDC1-independent but requires other phosphorylated proteins. Collectively, our study not only reveals the significance of MRN complex in repairing meiotic DSBs but also discovers a unique mechanism that recruits MRN complex to SPO11-linked DSB sites.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Ciclo Celular / Proteínas de Unión al ADN / Reparación del ADN / Endodesoxirribonucleasas / Roturas del ADN de Doble Cadena / Meiosis Límite: Animals / Humans / Male Idioma: En Revista: Cell Death Differ Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Ciclo Celular / Proteínas de Unión al ADN / Reparación del ADN / Endodesoxirribonucleasas / Roturas del ADN de Doble Cadena / Meiosis Límite: Animals / Humans / Male Idioma: En Revista: Cell Death Differ Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido