Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

作者：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; Bonafe Luisa; Brunstom Hernandez Janice E; Buckard Johannes A; Chitayat David; Chong Wui K; Cordelli Duccio M; Ferreira Patrick; Fluss Joel

来源：Nature Genetics, 2012, 44(3): 338-U1604.

DOI：10.1038/ng.1084

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 gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha 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.

• 出版日期2012-3