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TRF2 promotes, remodels and protects telomeric Holliday junctions
Author(s) -
Poulet Anaïs,
Buisson Rémi,
FaivreMoskalenko Cendrine,
Koelblen Mélanie,
Amiard Simon,
Montel Fabien,
CuestaLopez Santiago,
Bornet Olivier,
Guerlesquin Françoise,
Godet Thomas,
Moukhtar Julien,
Argoul Françoise,
Déclais AnneCécile,
Lilley David M J,
Ip Stephen C Y,
West Stephen C,
Gilson Eric,
GiraudPanis MarieJosèphe
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.11
Subject(s) - holliday junction , biology , telomere , microbiology and biotechnology , cleavage (geology) , homologous recombination , dna , biophysics , genetics , paleontology , fracture (geology)
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.