期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms8676
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资金
- Ministerio de Economia y Competitividad (MINECO) [BFU2012-39521, BFU2012-33960, SAF2011-28842-C02-01, BFU2014-53681-P, BFU2010-18965]
- National Institute of Health [NS-37956, CA-21765]
- CCSG [P30 CA 21765]
- Associazione Italiana per Ricerca sul Cancro
- European Research Council [614541]
- Association for International Cancer Research [13-0026]
- Giovanni Armenise Award
- Epigen Progetto Bandiera [4.7]
- Fondazione Telethon [GGP13071]
- European Community [241955]
- Swiss National Science Foundation
- Severo Ochoa FPI fellowship (MINECO)
- Marie Curie Action (COFUND) within the EU 7th Framework programme
- European Research Council (ERC) [614541] Funding Source: European Research Council (ERC)
CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63-deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death, and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63-deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination.
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