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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling
Nature Genetics, Volume 40, No. 2, Year 2008
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Description
Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT) - resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins - also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size. © 2008 Nature Publishing Group.
Authors & Co-Authors
Griffith, Elen
United Kingdom, Edinburgh
Western General Hospital
Walker, Sarah A.
United Kingdom, Brighton
Genome Damage and Stability Centre
Martin, Carol Anne
United Kingdom, Edinburgh
Western General Hospital
Vagnarelli, Paola
United Kingdom, Edinburgh
Wellcome Trust Centre for Cell Biology
Stiff, Tom
United Kingdom, Brighton
Genome Damage and Stability Centre
Vernay, Bertrand
United Kingdom, Edinburgh
Western General Hospital
Sanna, Nouriya Al
Saudi Arabia, Dhahran
Johns Hopkins Aramco Healthcare
Saggar, Anand
United Kingdom, London
St George’s, University of London
Hamel, Ben C.J.
Netherlands, Nijmegen
Radboud University Medical Center
Earnshaw, William C.
United Kingdom, Edinburgh
Wellcome Trust Centre for Cell Biology
Jeggo, Penny A.
United Kingdom, Brighton
Genome Damage and Stability Centre
Jackson, Andrew P.
United Kingdom, Edinburgh
Western General Hospital
O'Driscoll, Mark C.
United Kingdom, Brighton
Genome Damage and Stability Centre
Statistics
Citations: 318
Authors: 13
Affiliations: 6
Identifiers
Doi:
10.1038/ng.2007.80
ISSN:
10614036
e-ISSN:
15461718
Research Areas
Cancer
Genetics And Genomics