CEP152 is a genome maintenance protein disrupted in Seckel syndrome

ISSN
1061-4036
Date Issued
2011
Author(s)
Kalay, Ersan
Aslan, Yakup
Brown, Karen E.
Pohl, Esther
Bicknell, Louise S.
Kayserili, Hülya
Tuysuz, Beyhan
Nürnberg, Gudrun
Kiess, Wieland
Koegl, Manfred
Baessmann, Ingelore
Buruk, Kurtulus
Toraman, Bayram
Kayipmaz, Saadettin
Kul, Sibel
Ikbal, Mevlit
Turner, Daniel J.
Taylor, Martin S.
Aerts, Jan
Scott, Carol
Milstein, Karen
Dollfus, Helene
Wieczorek, Dagmar
Brunner, Han G.
Hurles, Matthew
Jackson, Andrew P.
Rauch, Anita
Nürnberg, Peter
Karaguzel, Ahmet
DOI
10.1038/ng.725
Abstract
Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation.