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A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair

  • Authors:
    • Hwa Jin Jung
    • Hye Lim Kim
    • Yeo Jin Kim
    • Jong-Il Weon
    • Young Rok Seo
  • View Affiliations / Copyright

    Affiliations: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA, Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Jung-gu, Seoul 100-715, Republic of Korea, Department of Safety Engineering, Dongguk University, Gyeongju, Gyeongbuk 780-714, Republic of Korea
    Copyright: © Jung et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1581-1586
    |
    Published online on: July 11, 2013
       https://doi.org/10.3892/or.2013.2613
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Abstract

Organic selenium compounds have been documented to play a role in cancer prevention. Our previous study showed that selenomethionine (SeMet) induces p53 activation without genotoxic effects including apoptosis and cell cycle arrest. In this study, we investigated the mechanism by which organic selenium compounds promote p53-mediated base excision repair (BER) activity. Our data demonstrated for the first time that the interaction between growth arrest and DNA damage-inducible protein 45A (Gadd45a), which is a p53-activated downstream gene, and two BER-mediated repair proteins, proliferating cell nuclear antigen (PCNA) and apurinic/apyrimidinic endonuclease (APE1/Ref-1), was significantly increased in a p53-dependent manner following treatment with organic selenium compounds. Furthermore, we observed that the activity of APE1 was significantly increased in a p53-dependent manner in response to the organic selenium compounds. These results suggest that BER activity is dependent on wild-type p53 activity and is mediated by the modulation of protein interactions between Gadd45a and repair proteins in response to organic selenium compounds. We propose that p53-dependent BER activity is a distinct chemopreventive mechanism mediated by organic selenium compounds, and that this may provide insight into the development of effective chemopreventive strategies against various oxidative stresses that contribute to a variety of human diseases, particularly cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Jung HJ, Kim HL, Kim YJ, Weon J and Seo YR: A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair. Oncol Rep 30: 1581-1586, 2013.
APA
Jung, H.J., Kim, H.L., Kim, Y.J., Weon, J., & Seo, Y.R. (2013). A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair. Oncology Reports, 30, 1581-1586. https://doi.org/10.3892/or.2013.2613
MLA
Jung, H. J., Kim, H. L., Kim, Y. J., Weon, J., Seo, Y. R."A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair". Oncology Reports 30.4 (2013): 1581-1586.
Chicago
Jung, H. J., Kim, H. L., Kim, Y. J., Weon, J., Seo, Y. R."A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair". Oncology Reports 30, no. 4 (2013): 1581-1586. https://doi.org/10.3892/or.2013.2613
Copy and paste a formatted citation
x
Spandidos Publications style
Jung HJ, Kim HL, Kim YJ, Weon J and Seo YR: A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair. Oncol Rep 30: 1581-1586, 2013.
APA
Jung, H.J., Kim, H.L., Kim, Y.J., Weon, J., & Seo, Y.R. (2013). A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair. Oncology Reports, 30, 1581-1586. https://doi.org/10.3892/or.2013.2613
MLA
Jung, H. J., Kim, H. L., Kim, Y. J., Weon, J., Seo, Y. R."A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair". Oncology Reports 30.4 (2013): 1581-1586.
Chicago
Jung, H. J., Kim, H. L., Kim, Y. J., Weon, J., Seo, Y. R."A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair". Oncology Reports 30, no. 4 (2013): 1581-1586. https://doi.org/10.3892/or.2013.2613
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