Acetylation regulates WRN catalytic activities and affects base excision DNA repair.
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.
Muftuoglu
Meltem
M
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
Kusumoto
Rika
R
Speina
Elzbieta
E
Beck
Gad
G
Cheng
Wen-Hsing
WH
Bohr
Vilhelm A
VA
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
D011994:Recombinant Proteins; D004247:DNA; D051548:Histone Acetyltransferases; D005090:Exodeoxyribonucleases; D005092:Exonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase