title: Acetylation regulates WRN catalytic activities and affects base excision DNA repair.
abstract: BACKGROUND
  The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone acetyltransferases is of key interest because of its potential importance in aging, DNA repair and transcription.
  
  
  RESULTS
  Here, we have investigated the p300 acetylation mediated changes on the function of WRN in base excision DNA repair (BER). We show that acetylation of WRN increases in cells treated with methyl methanesulfonate (MMS), suggesting that acetylation of WRN may play a role in response to DNA damage. This hypothesis is consistent with our findings that acetylation of WRN stimulates its catalytic activities in vitro and in vivo, and that acetylated WRN enhances pol beta-mediated strand displacement DNA synthesis more than unacetylated WRN. Furthermore, we show that cellular exposure to the histone deacetylase inhibitor sodium butyrate stimulates long patch BER in wild type cells but not in WRN depleted cells, suggesting that acetylated WRN participates significantly in this process.
  
  
  CONCLUSIONS
  Collectively, these results provide the first evidence for a specific role of p300 mediated WRN acetylation in regulating its function during BER.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
authors.forename: Meltem
authors.initials: M
authors.lastname: Muftuoglu
authors.forename: Rika
authors.initials: R
authors.lastname: Kusumoto
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Speina
authors.forename: Gad
authors.initials: G
authors.lastname: Beck
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D000375:Aging; D002384:Catalysis; D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004260:DNA Repair; D005090:Exodeoxyribonucleases / Q000737:chemistry* / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D053484:RecQ Helicases / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D014158:Transcription, Genetic; D000071657:Werner Syndrome Helicase
chemical_list: D011994:Recombinant Proteins; D004247:DNA; D051548:Histone Acetyltransferases; D005090:Exodeoxyribonucleases; D005092:Exonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase