CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination
Entity
UAM. Departamento de BiologíaPublisher
Nature Publishing GroupDate
2015-07-09Citation
10.1038/ncomms8676
Nature Communications 6 (2015): 8676
ISSN
2041-1723 (online)DOI
10.1038/ncomms8676Funded by
T.H.S., J.L., J.S. and I.R. are supported by the Ministerio de Economía y Competitividad (MINECO; T.H.S.: BFU2012-39521, J.L.: BFU2012-33960, J.A.S.: SAF2011-28842-C02-01, BFU2014-53681-P and I.R.: BFU2010-18965); P.J.M. is supported by National Institute of Health (NS-37956, CA-21765,) and the CCSG (P30 CA-21765), V.C. is funded by the Associazione Italiana per Ricerca sul Cancro, the European Research Council consolidator grant (614541) and the Association for International Cancer Research (13-0026); the Giovanni Armenise Award was awarded to V.C., the Epigen Progetto Bandiera (4.7) and the Fondazione Telethon (GGP13071); and U.W. is supported by the European Community’s Seventh Framework Programme FP7/ 2009 under grant agreement number 241955 (SYSCILIA), P.A.K. was supported by an Early Postdoc Mobility fellowship from the Swiss National Science Foundation, B.T. by a Severo Ochoa FPI fellowship (MINECO) and M.M. by a Marie Curie Action (COFUND) within the EU 7th Framework programmeProject
Gobierno de España. BFU2012-39521; Gobierno de España. BFU2012-33960; Gobierno de España. SAF2011-28842-C02-01; Gobierno de España. BFU2014-53681-P; Gobierno de España. BFU2010-18965; info:eu-repo/grantAgreement/EC/FP7/241955Editor's Version
http://dx.doi.org/10.1038/ncomms8676Subjects
Protein cep63; Centrosome; Chromosome structure; Microcephaly; Meiotic recombination; Biología y Biomedicina / BiologíaNote
Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMRights
© 2015 Macmillan Publishers LimitedAbstract
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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Google Scholar:Marjanović, Marko
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Gómez Lencero, Rocío
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Suja Sánchez, José Ángel
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