title: PARP1 Is a TRF2-associated poly(ADP-ribose)polymerase and protects eroded telomeres.
abstract: Poly(ADP-ribose)polymerase 1 (PARP1) is well characterized for its role in base excision repair (BER), where it is activated by and binds to DNA breaks and catalyzes the poly(ADP-ribosyl)ation of several substrates involved in DNA damage repair. Here we demonstrate that PARP1 associates with telomere repeat binding factor 2 (TRF2) and is capable of poly(ADP-ribosyl)ation of TRF2, which affects binding of TRF2 to telomeric DNA. Immunostaining of interphase cells or metaphase spreads shows that PARP1 is detected sporadically at normal telomeres, but it appears preferentially at eroded telomeres caused by telomerase deficiency or damaged telomeres induced by DNA-damaging reagents. Although PARP1 is dispensable in the capping of normal telomeres, Parp1 deficiency leads to an increase in chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA in primary murine cells after induction of DNA damage. Our results suggest that upon DNA damage, PARP1 is recruited to damaged telomeres, where it can help protect telomeres against chromosome end-to-end fusions and genomic instability.
authors.affiliation: Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6445, USA.
authors.forename: Marla
authors.initials: M
authors.lastname: Gomez
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Valérie
authors.initials: V
authors.lastname: Schreiber
authors.forename: John
authors.initials: J
authors.lastname: Dunlap
authors.forename: Françoise
authors.initials: F
authors.lastname: Dantzer
authors.forename: Yisong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yie
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002875:Chromosomes / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D019281:Dimerization; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D016615:Telomere / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*
chemical_list: D035341:Telomeric Repeat Binding Protein 2; D004247:DNA; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases