Telomere Science Library

Publications, Presentations, and Videos
about the Nobel-Prize Winning Science of Telomere Biology

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

Authors: Marko M. Marjanović, Carlos C. Sánchez-Huertas, Berta B. Terré, Rocío R. Gómez, Jan Frederik JF. Scheel, Sarai S. Pacheco, Philip A PA. Knobel, Ana A. Martínez-Marchal, Suvi S. Aivio, Lluís L. Palenzuela, Uwe U. Wolfrum, Peter J PJ. McKinnon, José A JA. Suja, Ignasi I. Roig, Vincenzo V. Costanzo, Jens J. Lüders, Travis H TH. Stracker
Published: 07/09/2015, Nature communications


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.

PubMed Full Text