Naslov
CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination

Autori
Marjanović, Marko ; Sanchez-Huertas, Carlos ; Terre, Berta ; Gomez, Rocio ; Scheel, Jan Frederik ; Pacheco, Sarai ; Knobel, Philip ; Martinez-Marchal, Ana ; Aivio, Suvi ; Palenzuela, Lluis ; Wolfrum, Uwe ; McKinnon, Peter ; Suja, Jose ; Roig, Ignasi ; Costanzo, Vincenzo ; Luders, Jens ; Stracker, Travis

Izvornik
Nature Communications (2041-1723) 6 (2015); 7676-1

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
microcephaly ; DNA damage ; centrosome ; meiosis

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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