title: The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres.
abstract: The stability of mammalian telomeres depends upon TRF2, which prevents inappropriate repair and checkpoint activation. By using a plasmid integration assay in yeasts carrying humanized telomeres, we demonstrated that TRF2 possesses the intrinsic property to both stimulate initial homologous recombination events and to prevent their resolution via its basic N-terminal domain. In human cells, we further showed that this TRF2 domain prevents telomere shortening mediated by the resolvase-associated protein SLX4 as well as GEN1 and MUS81, 2 different types of endonucleases with resolvase activities. We propose that various types of resolvase activities are kept in check by the basic N-terminal domain of TRF2 in order to favor an accurate repair of the stalled forks that occur during telomere replication.
authors.affiliation: a Institute for Research on Cancer and Aging, Nice (IRCAN); CNRS UMR7284/INSERM U1081; Faculty of Medicine; Nice, France.
authors.forename: Adélaïde
authors.initials: A
authors.lastname: Saint-Léger
authors.forename: Melanie
authors.initials: M
authors.lastname: Koelblen
authors.forename: Livia
authors.initials: L
authors.lastname: Civitelli
authors.forename: Amadou
authors.initials: A
authors.lastname: Bah
authors.forename: Nadir
authors.initials: N
authors.lastname: Djerbi
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Giraud-Panis
authors.forename: Arturo
authors.initials: A
authors.lastname: Londoño-Vallejo
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Ascenzioni
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D057809:HEK293 Cells; D045565:Holliday Junction Resolvases / Q000378:metabolism; D006801:Humans; D010957:Plasmids; D045522:Recombinases / Q000378:metabolism; D011995:Recombination, Genetic; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D045522:Recombinases; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D016159:Tumor Suppressor Protein p53; D004720:Endonucleases; C498772:MUS81 protein, human; C542319:SLX4 protein, human; C533748:GEN1 protein, human; D045565:Holliday Junction Resolvases
keywords: TRF2; recombination; shelterin; telomere