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Determinants of Photolyase's DNA Repair Mechanism in Mesophiles and Extremophiles.

Publication ,  Journal Article
Rousseau, BJG; Shafei, S; Migliore, A; Stanley, RJ; Beratan, DN
Published in: Journal of the American Chemical Society
February 2018

Light-driven DNA repair by extremophilic photolyases is of tremendous importance for understanding the early development of life on Earth. The mechanism for flavin adenine dinucleotide repair of DNA lesions is the subject of debate and has been studied mainly in mesophilic species. In particular, the role of adenine in the repair process is poorly understood. Using molecular docking, molecular dynamics simulations, electronic structure calculations, and electron tunneling pathways analysis, we examined adenine's role in DNA repair in four photolyases that thrive at different temperatures. Our results indicate that the contribution of adenine to the electronic coupling between the flavin and the cyclobutane pyrimidine dimer lesion to be repaired is significant in three (one mesophilic and two extremophilic) of the four enzymes studied. Our analysis suggests that thermophilic and hyperthermophilic photolyases have evolved structurally to preserve the functional position (and thus the catalytic function) of adenine at their high temperatures of operation. Water molecules can compete with adenine in establishing the strongest coupling pathway for the electron transfer repair process, but the adenine contribution remains substantial. The present study also reconciles prior seemingly contradictory conclusions on the role of adenine in mesophile electron transfer repair reactions, showing how adenine-mediated superexchange is conformationally gated.

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Published In

Journal of the American Chemical Society

DOI

EISSN

1520-5126

ISSN

0002-7863

Publication Date

February 2018

Volume

140

Issue

8

Start / End Page

2853 / 2861

Related Subject Headings

  • Pyrimidines
  • Models, Molecular
  • General Chemistry
  • Dinitrocresols
  • Deoxyribodipyrimidine Photo-Lyase
  • DNA Repair
  • Adenine
  • 40 Engineering
  • 34 Chemical sciences
  • 03 Chemical Sciences
 

Citation

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Rousseau, B. J. G., Shafei, S., Migliore, A., Stanley, R. J., & Beratan, D. N. (2018). Determinants of Photolyase's DNA Repair Mechanism in Mesophiles and Extremophiles. Journal of the American Chemical Society, 140(8), 2853–2861. https://doi.org/10.1021/jacs.7b11926
Rousseau, Benjamin J. G., Shoresh Shafei, Agostino Migliore, Robert J. Stanley, and David N. Beratan. “Determinants of Photolyase's DNA Repair Mechanism in Mesophiles and Extremophiles.Journal of the American Chemical Society 140, no. 8 (February 2018): 2853–61. https://doi.org/10.1021/jacs.7b11926.
Rousseau BJG, Shafei S, Migliore A, Stanley RJ, Beratan DN. Determinants of Photolyase's DNA Repair Mechanism in Mesophiles and Extremophiles. Journal of the American Chemical Society. 2018 Feb;140(8):2853–61.
Rousseau, Benjamin J. G., et al. “Determinants of Photolyase's DNA Repair Mechanism in Mesophiles and Extremophiles.Journal of the American Chemical Society, vol. 140, no. 8, Feb. 2018, pp. 2853–61. Epmc, doi:10.1021/jacs.7b11926.
Rousseau BJG, Shafei S, Migliore A, Stanley RJ, Beratan DN. Determinants of Photolyase's DNA Repair Mechanism in Mesophiles and Extremophiles. Journal of the American Chemical Society. 2018 Feb;140(8):2853–2861.
Journal cover image

Published In

Journal of the American Chemical Society

DOI

EISSN

1520-5126

ISSN

0002-7863

Publication Date

February 2018

Volume

140

Issue

8

Start / End Page

2853 / 2861

Related Subject Headings

  • Pyrimidines
  • Models, Molecular
  • General Chemistry
  • Dinitrocresols
  • Deoxyribodipyrimidine Photo-Lyase
  • DNA Repair
  • Adenine
  • 40 Engineering
  • 34 Chemical sciences
  • 03 Chemical Sciences