Inhibitory action of C22-fatty acids on DNA polymerases and DNA topoisomerases

  • Authors:
    • Yuko Yonezawa
    • Takahiko Hada
    • Keisuke Uryu
    • Hiroshi Iijima
    • Hiromi Yoshida
    • Yoshiyuki Mizushina
  • View Affiliations

  • Published online on: October 1, 2006     https://doi.org/10.3892/ijmm.18.4.583
  • Pages: 583-588
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Abstract

We reported previously that unsaturated linear-chain fatty acids of the cis-configuration with a C18-hydrocarbon chain such as linoleic acid (cis-9, 12-octadecadienoic acid, C18:2) could potently inhibit the activity of mammalian DNA polymerases (Biochim Biophys Acta 1308: 256-262, 1996). In this study, we investigated the inhibitory effects of cis-type C22-fatty acids including cis-7,10,13,16,19-docosapentaenoic acid (DPA, C22:5) and cis-4,7,10,13,16,19-docosahexaenoic acid (DHA, C22:6) on mammalian DNA polymerases and human DNA topoisomerases. Cis-13,16-docosadienoic acid (C22:2) was the strongest inhibitor of both DNA polymerases and topoisomerases of all C22-fatty acids tested. The inhibitory tendency by the fatty acids on DNA polymerases was the same as that of DNA topoisomerases, and the second strongest inhibitor was cis-13,16,19-docosatrienoic acid (C22:3). The energy-minimized three-dimensional structures of the fatty acids were calculated and it was found that a length of 19-21 Å and width of more than 7 Å in C22-fatty acid structure were important for enzyme inhibition. The three-dimensional structure of the active site of both DNA polymerases and topoisomerases must have a pocket to join C22:2, and this pocket was 19.41 Å long and 9.58 Å wide.

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October 2006
Volume 18 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yonezawa Y, Hada T, Uryu K, Iijima H, Yoshida H and Mizushina Y: Inhibitory action of C22-fatty acids on DNA polymerases and DNA topoisomerases. Int J Mol Med 18: 583-588, 2006
APA
Yonezawa, Y., Hada, T., Uryu, K., Iijima, H., Yoshida, H., & Mizushina, Y. (2006). Inhibitory action of C22-fatty acids on DNA polymerases and DNA topoisomerases. International Journal of Molecular Medicine, 18, 583-588. https://doi.org/10.3892/ijmm.18.4.583
MLA
Yonezawa, Y., Hada, T., Uryu, K., Iijima, H., Yoshida, H., Mizushina, Y."Inhibitory action of C22-fatty acids on DNA polymerases and DNA topoisomerases". International Journal of Molecular Medicine 18.4 (2006): 583-588.
Chicago
Yonezawa, Y., Hada, T., Uryu, K., Iijima, H., Yoshida, H., Mizushina, Y."Inhibitory action of C22-fatty acids on DNA polymerases and DNA topoisomerases". International Journal of Molecular Medicine 18, no. 4 (2006): 583-588. https://doi.org/10.3892/ijmm.18.4.583