The origin recognition complex localizes to telomere repeats and prevents telomere-circle formation.
Curr Biol
; 17(22): 1989-95, 2007 Nov 20.
Article
em En
| MEDLINE
| ID: mdl-18006317
ABSTRACT
Chromosome ends are maintained by telomere-repeat-binding factors (TRFs) that coordinate DNA end protection with telomere replication. The origin recognition complex (ORC) coordinates bidirectional DNA replication at most chromosomal sites, but it is also known to function in transcriptional silencing, heterochromatin formation, and sister-chromatid cohesion. We now show that ORC localizes to telomere repeats and contributes to telomere maintenance. We found that ORC subunits can be affinity purified with telomere-repeat DNA along with other components of the known "shelterin" complex. ORC subunits colocalized with telomere-repeat foci and coimmunoprecipitated with TRF2 but not TRF2 lacking its amino-terminal basic domain (TRF2DeltaB). ORC2 depletion or hypomorphic cell lines caused a loss of telomere-repeat signal intensity and the appearance of dysfunctional telomeres, including telomere-signal-free ends and telomere-repeat-containing double minutes. Two-dimensional agarose gel electrophoresis revealed that ORC2 depletion increased telomere circle formation, comparable to the overexpression of TRF2DeltaB. A similar increase in telomere circle formation was induced by hydroxyurea treatment, providing evidence that replication stress produces telomere circles. These findings suggest that ORC recruitment by TRF2 contributes to telomere integrity by facilitating efficient telomere DNA replication and preventing the generation of telomere-repeat-containing circles.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sequências Repetitivas de Ácido Nucleico
/
Aberrações Cromossômicas
/
Telômero
/
Complexo de Reconhecimento de Origem
Limite:
Humans
Idioma:
En
Revista:
Curr Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos