title: SIRT6 promotes DNA repair under stress by activating PARP1.
abstract: Sirtuin 6 (SIRT6) is a mammalian homolog of the yeast Sir2 deacetylase. Mice deficient for SIRT6 exhibit genome instability. Here, we show that in mammalian cells subjected to oxidative stress SIRT6 is recruited to the sites of DNA double-strand breaks (DSBs) and stimulates DSB repair, through both nonhomologous end joining and homologous recombination. Our results indicate that SIRT6 physically associates with poly[adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP1) and mono-ADP-ribosylates PARP1 on lysine residue 521, thereby stimulating PARP1 poly-ADP-ribosylase activity and enhancing DSB repair under oxidative stress.
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Mao
authors.forename: Christopher
authors.initials: C
authors.lastname: Hine
authors.forename: Xiao
authors.initials: X
authors.lastname: Tian
authors.forename: Michael
authors.initials: M
authors.lastname: Van Meter
authors.forename: Matthew
authors.initials: M
authors.lastname: Au
authors.forename: Amita
authors.initials: A
authors.lastname: Vaidya
authors.forename: Andrei
authors.initials: A
authors.lastname: Seluanov
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
mesh_terms: D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D017354:Point Mutation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; C499320:PARP1 protein, human; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C516592:SIRT6 protein, human; D037761:Sirtuins; D010269:Paraquat