SIRT6 Promotes DNA Repair Under Stress by Activating PARP1

• Published in: Science (American Association for the Advancement of Science) Vol. 332; no. 6036; pp. 1443 - 1446
• Main Authors: Mao, Zhiyong, Hine, Christopher, Tian, Xiao, Van Meter, Michael, Au, Matthew, Vaidya, Amita, Seluanov, Andrei, Gorbunova, Vera
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 17.06.2011; The American Association for the Advancement of Science
• Subjects: Adenosine diphosphate; Animals; Antibodies; Biological and medical sciences; Cell Line; Cell lines; Deoxyribonucleic acid; Diphosphates; DNA; DNA - metabolism; DNA Breaks, Double-Stranded; DNA damage; DNA Repair; Enzymes; Fibroblasts; Fundamental and applied biological sciences. Psychology; Genetic mutation; genome; Genomes; homologous recombination; Humans; Joining; Lysine; Mammals; Mice; Mice, Knockout; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Oxidative Stress; Paraquat - pharmacology; Phenotypes; Point Mutation; Poly (ADP-Ribose) Polymerase-1; Poly Adenosine Diphosphate Ribose - metabolism; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Proteins; Recombination, Genetic; Repair; Residues; Signal Transduction; Sirtuins - genetics; Sirtuins - metabolism; Stress response; Stresses; Transfection; Yeasts; Double strand break; Oxidative stress; Vertebrata; Mammalia; Mouse; DNA; Rodentia; Repair; Sirtuin
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1202723

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.