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Acetylation Regulates WRN Catalytic Activities and Affects Base Excision DNA Repair (2007)
| Citations: | 9 - 1 self |
BibTeX
@MISC{Muftuoglu07acetylationregulates,
author = {Meltem Muftuoglu and Rika Kusumoto and Elzbieta Speina and Gad Beck and Wen-hsing Cheng and Vilhelm A},
title = {Acetylation Regulates WRN Catalytic Activities and Affects Base Excision DNA Repair},
year = {2007}
}
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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. Methodology/Principal Findings: 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 b-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. Conclusion/Significance: Collectively, these results provide the first evidence for a specific role of p300 mediated WRN acetylation in regulating its function during BER.
Keyphrases
acetylation regulates wrn catalytic activity affect base excision dna repair dna repair dna damage methodology principal finding wild type cell conclusion significance p300 acetylation key interest b-mediated strand displacement dna synthesis werner protein dna metabolic process cellular exposure possible regulation potential importance first evidence unacetylated wrn base excision dna repair wrn acetylation wrn enhances disorder werner syndrome catalytic activity wrn participates histone acetyltransferases specific role post-translational modification methyl methanesulfonate wrn increase
