Naslov
Murine Cep63 is required for brain development and male fertility

Autori
Marjanović, Marko ; Brown, Nicola ; Sanchez- Huertas, Carlos ; Costanzo, Vincenzo ; Luders, Jens ; Stracker, Travis

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
The Microtubule Cytoskeleton in Development and Disease

Mjesto i datum
Barcelona, Španjolska, 18.03.2013. - 20.03.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
centrosome; microcephaly; meiosis; mitosis

Sažetak
Significant overlap in the pathology of human diseases caused by defects in the DNA damage response (DDR) or centrosome homeostasis suggest they may have similar underlying mechanisms. Seckel syndrome is caused by the deficiency in the DDR proteihs ATR or CtIP or the centrosomeal proteinst PCNT or CenpJ and patients present with severe dwarfism, microcephaly, mental retardation and metabolic abnormalities. We have been investigating the functions of Cep63, a centrosomal protein that was indentified as an ATR substrate and has recentely been implicated in Seckel syndrome, as it provides a potential link between the DDR and the centrosome. To determine the consequences of Cep63 deficiency, we have generated animals with a genetrap that inhibits expression of all known isoforms of Cep63. We find that the DNA damage response is intact, as cells from these animals did not exhibit sensitivity to DNA damage or checkpoint abnormalities. However, Cep63 is required for the recruitment of essential centriole duplication factors, including Cep152 and Sas- 6, and Cep63-deficient cells display abnormal centrosome configurations. Animals lacking Cep563 are runted and show severe defects in testicular development. We propose that Cep63 animals provide a model system for understanding the etiology of human microcephaly and implicate the centrosomal functions of Cep63 in male fertility. Current results from the ongoing characterization of these animals will be presented

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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