Journal article
CEP152 is a genome maintenance protein disrupted in Seckel syndrome
E Kalay, G Yigit, Y Aslan, KE Brown, E Pohl, LS Bicknell, H Kayserili, Y Li, B Tüysüz, G Nürnberg, W Kiess, M Koegl, I Baessmann, K Buruk, B Toraman, S Kayipmaz, S Kul, M Ikbal, DJ Turner, MS Taylor Show all
Nature Genetics | NATURE PUBLISHING GROUP | Published : 2011
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. © 2011 Nature America, Inc. All rights reserved.
Grants
Awarded by Lister Institute of Preventive Medicine
Funding Acknowledgements
We thank all family members who participated in this study, E. Milz, A. Alver and A. Coffey for excellent technical assistance, F. Kokocinski and A. Palotie for experimental design, and C. Kubisch, B. Wirth and K. Boss for critical reading the manuscript. The CINP antibody was a kind gift from D. Cortez (Nashville, Tennessee, USA). This work was supported by the German Federal Ministry of Education and Research (BMBF) by grant numbers 01GM0880 (SKELNET) and 01GM0801 (E-RARE network CRANIRARE) to B.W., the Karadeniz Technical University Research Fund by grant numbers 2008.114.001.02 and 2008.114.001.12 to E.K., the Medical Research Council and Lister Institute to A.P.J. and by the Wellcome Trust, grant 077014/Z/05/Z.