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TRF2 promotes, remodels and protects telomeric Holliday junctions.
- Source :
-
The EMBO journal [EMBO J] 2009 Mar 18; Vol. 28 (6), pp. 641-51. Date of Electronic Publication: 2009 Feb 05. - Publication Year :
- 2009
-
Abstract
- The ability of the telomeric DNA-binding protein, TRF2, to stimulate t-loop formation while preventing t-loop deletion is believed to be crucial to maintain telomere integrity in mammals. However, little is known on the molecular mechanisms behind these properties of TRF2. In this report, we show that TRF2 greatly increases the rate of Holliday junction (HJ) formation and blocks the cleavage by various types of HJ resolving activities, including the newly identified human GEN1 protein. By using potassium permanganate probing and differential scanning calorimetry, we reveal that the basic domain of TRF2 induces structural changes to the junction. We propose that TRF2 contributes to t-loop stabilisation by stimulating HJ formation and by preventing resolvase cleavage. These findings provide novel insights into the interplay between telomere protection and homologous recombination and suggest a general model in which TRF2 maintains telomere integrity by controlling the turnover of HJ at t-loops and at regressed replication forks.
- Subjects :
- Bacteria enzymology
Base Pairing
Base Sequence
Biological Assay
Histidine metabolism
Holliday Junction Resolvases metabolism
Humans
Molecular Sequence Data
Potassium Permanganate pharmacology
Protein Binding drug effects
Protein Structure, Tertiary
Recombinases metabolism
Saccharomyces cerevisiae enzymology
Telomeric Repeat Binding Protein 2 chemistry
DNA, Cruciform metabolism
Telomere metabolism
Telomeric Repeat Binding Protein 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2075
- Volume :
- 28
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 19197240
- Full Text :
- https://doi.org/10.1038/emboj.2009.11