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PMID: 15007108 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Telomere-bound TRF1 and TRF2 stall the replication fork at telomeric repeats.

Nucleic acids research ·Vol. 32 ·No. 5 ·2004-00-00 ·Pages 1627-37

Ohki R, Ishikawa F

Abstract

Vertebrate telomeres consist of tandem repeats of T2AG3 and associated proteins including the telomeric DNA-binding proteins, TRF1 and TRF2. It has been proposed that telomeres assume two interswitchable states, the open state that is accessible to various trans-acting factors and the closed state that excludes those factors. TRF1 and TRF2 are believed to promote the formation of the closed state. However, little is known about how those two states influence DNA replication. We analyzed the effects of TRF1 and TRF2 on telomeric replication both in vitro and in vivo. By exploiting the in vitro replication system of linear SV40 DNA, we found that telomeric repeats are a poor replication template. Moreover, the addition of recombinant TRF1 and TRF2 significantly stalled the replication fork progression at telomeric repeats. When TRF1 was overexpressed in HeLa cells, cells with 4N DNA content were accumulated. Furthermore, cytological analyses revealed that the replication focus overlapped with telomere signals at a significantly higher frequency in TRF1-overexpressing cells than in control cells. The results suggest that TRF1 and TRF2 exert inhibitory effects on replication fork progression.

MeSH Terms
Cell Cycle DNA Replication HeLa Cells Humans Repetitive Sequences, Nucleic Acid Telomere/chemistry,genetics,metabolism Telomeric Repeat Binding Protein 1/metabolism,physiology Telomeric Repeat Binding Protein 2/metabolism,physiology
Chemicals
Telomeric Repeat Binding Protein 1 Telomeric Repeat Binding Protein 2
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ohki Rieko
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Ishikawa Fuyuki
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkh309
Published
2004-00-00
Epub
2004-00-08
Pages
1627-37
Language
English
Region
England
NLM ID
0411011
PMCID
PMC390322
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkh309 PMC Full Text View journal details
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