Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus.
Nat Genet
; 44(3): 338-42, 2012 Jan 22.
Article
em En
| MEDLINE
| ID: mdl-22267198
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anormalidades Múltiplas
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Telômero
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Predisposição Genética para Doença
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Proteínas de Ligação a Telômeros
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Telangiectasia Retiniana
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido