title: Functional interaction between poly(ADP-Ribose) polymerase 2 (PARP-2) and TRF2: PARP activity negatively regulates TRF2.
abstract: The DNA damage-dependent poly(ADP-ribose) polymerase-2 (PARP-2) is, together with PARP-1, an active player of the base excision repair process, thus defining its key role in genome surveillance and protection. Telomeres are specialized DNA-protein structures that protect chromosome ends from being recognized and processed as DNA strand breaks. In mammals, telomere protection depends on the T(2)AG(3) repeat binding protein TRF2, which has been shown to remodel telomeres into large duplex loops (t-loops). In this work we show that PARP-2 physically binds to TRF2 with high affinity. The association of both proteins requires the N-terminal domain of PARP-2 and the myb domain of TRF2. Both partners colocalize at promyelocytic leukemia bodies in immortalized telomerase-negative cells. In addition, our data show that PARP activity regulates the DNA binding activity of TRF2 via both a covalent heteromodification of the dimerization domain of TRF2 and a noncovalent binding of poly(ADP-ribose) to the myb domain of TRF2. PARP-2(-/-) primary cells show normal telomere length as well as normal telomerase activity compared to wild-type cells but display a spontaneously increased frequency of chromosome and chromatid breaks and of ends lacking detectable T(2)AG(3) repeats. Altogether, these results suggest a functional role of PARP-2 activity in the maintenance of telomere integrity.
authors.affiliation: UPR 9003 du Centre National de la Recherche Scientifique, Université Louis Pasteur, Ecole Supérieure de Biotechnologie de Strasbourg, 67412 Illkirch Cedex, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Dantzer
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Giraud-Panis
authors.forename: Isabel
authors.initials: I
authors.lastname: Jaco
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Amé
authors.forename: Inès
authors.initials: I
authors.lastname: Schultz
authors.forename: Maria
authors.initials: M
authors.lastname: Blasco
authors.forename: Catherine-Elaine
authors.initials: CE
authors.lastname: Koering
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.forename: Josiane
authors.initials: J
authors.lastname: Ménissier-de Murcia
authors.forename: Gilbert
authors.initials: G
authors.lastname: de Murcia
authors.forename: Valérie
authors.initials: V
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002842:Chromatids / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000378:metabolism; D004247:DNA / Q000037:antagonists & inhibitors / Q000378:metabolism; D004249:DNA Damage; D005347:Fibroblasts; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D035341:Telomeric Repeat Binding Protein 2; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse; D019098:Telomerase