The origin recognition complex localizes to telomere repeats and prevents telomere-circle formation.

Zhong Deng, Jayaraju Dheekollu, Dominique Broccoli, Anindya Dutta, Paul M Lieberman
Author Information
  1. Zhong Deng: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

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.

Grants

  1. CA093606/NCI NIH HHS

MeSH Term

Chromosome Aberrations
HCT116 Cells
Humans
Origin Recognition Complex
Repetitive Sequences, Nucleic Acid
Telomere

Chemicals

Origin Recognition Complex

Word Cloud

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