Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

CEP152 is a genome maintenance protein disrupted in Seckel syndrome


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Clinical and molecular characterization of CEP152 Seckel subjects.
Figure 2: Characterization of CEP152 Seckel cells.

Accession codes


NCBI Reference Sequence


  1. Nyberg, K.A., Michelson, R.J., Putnam, C.W. & Weinert, T.A. Annu. Rev. Genet. 36, 617–656 (2002).

    Article  CAS  Google Scholar 

  2. Cimprich, K.A. & Cortez, D. Nat. Rev. Mol. Cell Biol. 9, 616–627 (2008).

    Article  CAS  Google Scholar 

  3. Bonner, W.M. et al. Nat. Rev. Cancer 8, 957–967 (2008).

    Article  CAS  Google Scholar 

  4. O'Driscoll, M., Ruiz-Perez, V.L., Woods, C.G., Jeggo, P.A. & Goodship, J.A. Nat. Genet. 33, 497–501 (2003).

    Article  CAS  Google Scholar 

  5. Murga, M. et al. Nat. Genet. 41, 891–898 (2009).

    Article  CAS  Google Scholar 

  6. Majewski, F. & Goecke, T. Am. J. Med. Genet. 12, 7–21 (1982).

    Article  CAS  Google Scholar 

  7. Rauch, A. et al. Science 319, 816–819 (2008).

    Article  CAS  Google Scholar 

  8. Griffith, E. et al. Nat. Genet. 40, 232–236 (2008).

    Article  CAS  Google Scholar 

  9. Guernsey, D.L. et al. Am. J. Hum. Genet. 87, 40–51 (2010).

    Article  CAS  Google Scholar 

  10. Andersen, J.S. et al. Nature 426, 570–574 (2003).

    Article  CAS  Google Scholar 

  11. Blachon, S. et al. Genetics 180, 2081–2094 (2008).

    Article  CAS  Google Scholar 

  12. Doxsey, S.J., Stein, P., Evans, L., Calarco, P.D. & Kirschner, M. Cell 76, 639–650 (1994).

    Article  CAS  Google Scholar 

  13. Lovejoy, C.A. et al. Proc. Natl. Acad. Sci. USA 106, 19304–19309 (2009).

    Article  CAS  Google Scholar 

  14. Liu, Q. et al. Genes Dev. 70, 1448–1459 (2000).

    Google Scholar 

  15. Marti, T.M., Hefner, E., Feeney, L., Natale, V. & Cleaver, J.E. Proc. Natl. Acad. Sci. USA 103, 9891–9896 (2006).

    Article  CAS  Google Scholar 

Download references


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.

Author information

Authors and Affiliations



The project was conceived and the experiments were planned by E.K. and B.W. We would like to note that Y.A. and K.E.B. had a comparable contribution to this study. The review of phenotypes and the sample collection were performed by B.W., E.K., Y.A., A.P.J., H.K., B. Tüysüz, W.K., B. Toraman., S. Kayipmaz, S. Kul, M.I., K.M., H.D., D.W., H.G.B. and A.R. Experiments were performed by E.K., G.Y., K.E.B., E.P., L.S.B., Y.L., M.K., I.B., K.B., D.J.T. and C.S. Data analysis was performed by B.W., E.K., G.N., P.N., A.K., J.A., M.S.T., M.H. and A.P.J. The manuscript was written by B.W., G.Y., E.K. and K.E.B. All aspects of the study were supervised by B.W.

Corresponding authors

Correspondence to Ersan Kalay or Bernd Wollnik.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8, Supplementary Tables 1–4 and Supplementary Methods (PDF 4081 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kalay, E., Yigit, G., Aslan, Y. et al. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet 43, 23–26 (2011).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing