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Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
Authors:Anderson Beverley H  Kasher Paul R  Mayer Josephine  Szynkiewicz Marcin  Jenkinson Emma M  Bhaskar Sanjeev S  Urquhart Jill E  Daly Sarah B  Dickerson Jonathan E  O'Sullivan James  Leibundgut Elisabeth Oppliger  Muter Joanne  Abdel-Salem Ghada M H  Babul-Hirji Riyana  Baxter Peter  Berger Andrea  Bonafé Luisa  Brunstom-Hernandez Janice E  Buckard Johannes A  Chitayat David  Chong Wui K  Cordelli Duccio M  Ferreira Patrick  Fluss Joel  Forrest Ewan H  Franzoni Emilio  Garone Caterina  Hammans Simon R  Houge Gunnar  Hughes Imelda  Jacquemont Sebastien  Jeannet Pierre-Yves  Jefferson Rosalind J  Kumar Ram  Kutschke Georg
Affiliation:Manchester Academic Health Science Centre, University of Manchester, Genetic Medicine, UK.
Abstract:
Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.
Keywords:
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