Abstract
Influence of AP endonuclease 1 deacetylation by protein deacetylase Sirt1 on DNA base excision repair
The Japan Radiation Research Society Annual Meeting Abstracts, pp.78-78
The Japan Radiation Research Society Annual Meeting Abstracts The 52nd Annual Meeting of the Japan Radiation Research Society
2009
DOI: 10.11513/jrrsabst.2009.0_78_2
Abstract
[Objective] NAD+-dependent protein deacetylase Sirt1 has been attracting attention as a longevity-regulating enzyme. Recent studies have shown that Sirt1 is involved in a myriad of physiological events including DNA repair of radiation-induced double strand brake. Base excision repair is one of DNA repair mechanisms that repairs DNA base damage, which is frequently generated by irradiation or oxidative stress and causes mutations. We investigated in this study (1) if AP endonuclease 1 (APE1), which is a constituent of base excision repair pathway, was a target of deacetylation by Sirt1, (2) how it affected APE1 function and base excision repair. [Methods and Results] Down-regulation of either APE1 or Sirt1 protein expression by RNAi in Hela cells promoted cell death induced by a DNA alkylating agent, methylmethane sulfonate (MMS), or hydrogen peroxide. Western blot analysis combined with immunoprecipitation revealed that APE1 interacted with Sirt1 in cells and was deacetylated by Sirt1 in vitro and in vivo. It was already reported that the interaction between APE1 and X-ray repair cross-complementing 1 (XRCC1) enhanced AP endonuclease activity of APE1. Resveratrol, a Sirt1 activator, promoted the APE1-XRCC1 interaction, and it was disappeared by Sirt1 RNAi. Furthermore, APE activity assay using XRCC1 immunoprecipitates from Hela cells treated with either nicotinamide, a Sirt1 inhibitor, or resveratrol showed that nicotinamide reduced APE activity and resveratrol increased it. [Conclusion] Results in this study suggested that (1) Sirt1 interacted with APE1 and deacetylated it; (2) APE1 deacetylation by Sirt1 promoted APE1-XRCC1 interaction and enhanced base excision repair activity, leading to the inhibition of cell death.
Details
- Title: Subtitle
- Influence of AP endonuclease 1 deacetylation by protein deacetylase Sirt1 on DNA base excision repair
- Creators
- Tohru Yamamori - Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido UniversityKaikobad Irani - University of Pittsburgh Medical Center
- Resource Type
- Abstract
- Publication Details
- The Japan Radiation Research Society Annual Meeting Abstracts, pp.78-78
- Conference
- The Japan Radiation Research Society Annual Meeting Abstracts The 52nd Annual Meeting of the Japan Radiation Research Society
- Publisher
- The Japanese Radiation Research Society
- DOI
- 10.11513/jrrsabst.2009.0_78_2
- Language
- English
- Date published
- 2009
- Academic Unit
- Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Cardiovascular Medicine
- Record Identifier
- 9984314277302771
Metrics
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