title: TRF2 promotes, remodels and protects telomeric Holliday junctions.
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.
authors.affiliation: Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Poulet
authors.forename: Rémi
authors.initials: R
authors.lastname: Buisson
authors.forename: Cendrine
authors.initials: C
authors.lastname: Faivre-Moskalenko
authors.forename: Mélanie
authors.initials: M
authors.lastname: Koelblen
authors.forename: Simon
authors.initials: S
authors.lastname: Amiard
authors.forename: Fabien
authors.initials: F
authors.lastname: Montel
authors.forename: Santiago
authors.initials: S
authors.lastname: Cuesta-Lopez
authors.forename: Olivier
authors.initials: O
authors.lastname: Bornet
authors.forename: Françoise
authors.initials: F
authors.lastname: Guerlesquin
authors.forename: Thomas
authors.initials: T
authors.lastname: Godet
authors.forename: Julien
authors.initials: J
authors.lastname: Moukhtar
authors.forename: Françoise
authors.initials: F
authors.lastname: Argoul
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Déclais
authors.forename: David M J
authors.initials: DM
authors.lastname: Lilley
authors.forename: Stephen C Y
authors.initials: SC
authors.lastname: Ip
authors.forename: Stephen C
authors.initials: SC
authors.lastname: West
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Giraud-Panis
mesh_terms: D001419:Bacteria / Q000201:enzymology; D020029:Base Pairing; D001483:Base Sequence; D001681:Biological Assay; D045566:DNA, Cruciform / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D045565:Holliday Junction Resolvases / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011196:Potassium Permanganate / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D045522:Recombinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D016615:Telomere / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D045566:DNA, Cruciform; D045522:Recombinases; D035341:Telomeric Repeat Binding Protein 2; D011196:Potassium Permanganate; D006639:Histidine; C533748:GEN1 protein, human; D045565:Holliday Junction Resolvases