Please use this identifier to cite or link to this item: http://buratest.brunel.ac.uk/handle/2438/8939
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dc.contributor.authorGriffith, E-
dc.contributor.authorWalker, S-
dc.contributor.authorMartin, CA-
dc.contributor.authorVagnarelli, P-
dc.contributor.authorStiff, T-
dc.contributor.authorVernay, B-
dc.contributor.authorAl Sanna, N-
dc.contributor.authorSaggar, A-
dc.contributor.authorHamel, B-
dc.contributor.authorEarnshaw, WC-
dc.contributor.authorJeggo, PA-
dc.contributor.authorJackson, AP-
dc.contributor.authorO'Driscoll, M-
dc.date.accessioned2014-08-20T09:03:17Z-
dc.date.available2014-08-20T09:03:17Z-
dc.date.issued2008-
dc.identifier.citationNature Genetics, 40(2), 232 - 236, 2008en_US
dc.identifier.issn1061-4036-
dc.identifier.urihttp://www.nature.com/ng/journal/v40/n2/full/ng.2007.80.htmlen
dc.identifier.urihttp://bura.brunel.ac.uk/handle/2438/8939-
dc.descriptionThis is the author's accepted manuscript. The final published article is available from www.nature.com at the link below.en_US
dc.description.abstractLarge 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.en_US
dc.description.sponsorshipMRC, CRUK, UK LRF, IACR, EU, and the Wellcome Trust.en_US
dc.languageeng-
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.subjectSeckel syndromeen_US
dc.subjectDNAen_US
dc.subjectATRen_US
dc.subjectPericentrinen_US
dc.titleMutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signalingen_US
dc.typeArticleen_US
dc.identifier.doihttp://dx.doi.org/10.1038/ng.2007.80-
pubs.organisational-data/Brunel-
pubs.organisational-data/Brunel/Brunel Staff by College/Department/Division-
pubs.organisational-data/Brunel/Brunel Staff by College/Department/Division/College of Health and Life Sciences-
pubs.organisational-data/Brunel/Brunel Staff by College/Department/Division/College of Health and Life Sciences/Dept of Life Sciences-
pubs.organisational-data/Brunel/Brunel Staff by College/Department/Division/College of Health and Life Sciences/Dept of Life Sciences/Biological Sciences-
pubs.organisational-data/Brunel/University Research Centres and Groups-
pubs.organisational-data/Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups-
pubs.organisational-data/Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups/Brunel Institute for Ageing Studies-
Appears in Collections:Biological Sciences
Dept of Life Sciences Research Papers

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