6533b856fe1ef96bd12b3151

RESEARCH PRODUCT

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

Ram L. KumarMarjo S. Van Der KnaapSanjeev S. BhaskarPierre-yves JeannetJohn B.p. StephensonGillian I. RiceJoel Victor FlussJames O'sullivanRaphael SchiffmannJohannes A. BuckardAndrea WhitneyRiyana Babul-hirjiCatheline VilainBeverley AndersonYanick J. CrowEmma M. JenkinsonGunnar HougeEwan ForrestVanessa WermenbolPeter BaxterSarah B. DalyMarcin SzynkiewiczJoanne MuterRosalind J. JeffersonWui K. ChongElisabeth Oppliger LeibundgutGabriela M. BaerlocherStefan MeyerStefan MeyerJonathan E. DickersonRamesh MehtaEmma WakelingSarah RisenJosé Pedro VieiraSakkubai NaiduAndrea BergerAndrea BergerCalvin SohJohn H. LivingstonDavid ChitayatStaffan LundbergSimon C. LovellLuís Catela NunesHelen StewartGraeme C.m. BlackJohn TolmieJanice E Brunstom-hernandezJill E. UrquhartJosephine MayerGhada M H Abdel-salemPaul R. KasherCharles Marques LourençoSimon HammansEmilio FranzoniCaterina GaroneCaterina GaroneKatrin ÕUnapDuccio Maria CordelliPrab PrabhakarKen K. NischalLuisa BonaféMichel PhilippartSébastien JacquemontPatrick FerreiraImelda HughesJon StoneGeorg Kutschke

subject

DNA polymeraseMolecular Sequence DataTelomere-Binding ProteinsHistones/metabolismHDE GENHDE NEU PEDCST complexCEREBRORETINAL MICROANGIOPATHY FAMILIAL SYNDROME CALCIFICATIONS CYSTS PROTEIN DNA LEUKOENCEPHALOPATHY EVOLUTION DEFECTSHistoneschemistry.chemical_compoundAbnormalities Multiple/geneticsGeneticsmedicineAbnormalities MultipleGenetic Predisposition to DiseaseGeneticsTelomere-binding proteinTelomere/pathologyddc:618biologyBase SequenceGenetic Predisposition to Disease/geneticsDNA replicationSequence Analysis DNATelomeremedicine.diseaseFlow CytometryTelomereCell biologyRetinal Telangiectasis/genetics/pathologychemistrySequence Analysis DNA/methodsbiology.proteinRetinal TelangiectasisPrimaseTelomere-Binding Proteins/geneticsDNADyskeratosis congenita

description

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.

yearjournalcountryeditionlanguage
2012-03-01Nature Genetics
10.1038/ng.1084https://hdl.handle.net/1871/42513