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 γ 3H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the I ±-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α, 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. © 2012 Nature America, Inc. All rights reserved.
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus / Anderson BH; Kasher PR; Mayer J; Szynkiewicz M; Jenkinson EM; Bhaskar SS; Urquhart JE; Daly SB; Dickerson JE; O'Sullivan J; Leibundgut EO; Muter J; Abdel-Salem GM; Babul-Hirji R; Baxter P; Berger A; Bonafé L; Brunstom-Hernandez JE; Buckard JA; Chitayat D; Chong WK; Cordelli DM; Ferreira P; Fluss J; Forrest EH; Franzoni E; Garone C; Hammans SR; Houge G; Hughes I; Jacquemont S; Jeannet PY; Jefferson RJ; Kumar R; Kutschke G; Lundberg S; Lourenço CM; Mehta R; Naidu S; Nischal KK; Nunes L; Ounap K; Philippart M; Prabhakar P; Risen SR; Schiffmann R; Soh C; Stephenson JB; Stewart H; Stone J; Tolmie JL; van der Knaap MS; Vieira JP;Vilain CN; Wakeling EL; Wermenbol V; Whitney A; Lovell SC; Meyer S; Livingston JH; Baerlocher GM; Black GC; Rice GI; Crow YJ. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 44:3(2012), pp. 338-342. [10.1038/ng.1084]
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
Cordelli DM;FRANZONI, EMILIO;Garone C;
2012
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 γ 3H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the I ±-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α, 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. © 2012 Nature America, Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
