Determinants of Photolyase’s DNA Repair Mechanism in Mesophiles and Extremophiles

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, th...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Chemical Society 2018-02, Vol.140 (8), p.2853-2861
Main Authors: Rousseau, Benjamin J. G, Shafei, Shoresh, Migliore, Agostino, Stanley, Robert J, Beratan, David N
Format: Article
Language:English
Subjects:
Adenine - chemistry
Adenine - metabolism
Deoxyribodipyrimidine Photo-Lyase - chemistry
Deoxyribodipyrimidine Photo-Lyase - metabolism
Dinitrocresols - chemistry
Dinitrocresols - metabolism
DNA Repair
Models, Molecular
Pyrimidines - chemistry
Pyrimidines - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.7b11926