Rousseau Benjamin J G, Migliore Agostino, Stanley Robert J, Beratan David N
Department of Chemistry, Duke University, Durham, North Carolina 27708, United States.
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520, United States.
J Phys Chem B. 2023 Apr 6;127(13):2941-2954. doi: 10.1021/acs.jpcb.3c00566. Epub 2023 Mar 22.
The comparative study of DNA repair by mesophilic and extremophilic photolyases helps us understand the evolution of these enzymes and their role in preserving life on our changing planet. The mechanism of repair of cyclobutane pyrimidine dimer lesions in DNA by electron transfer from the flavin adenine dinucleotide cofactor is the subject of intense interest. The role of adenine in mediating this process remains unresolved. Using microsecond molecular dynamics simulations, we find that adenine mediates the electron transfer in both mesophile and extremophile DNA photolyases through a similar mechanism. In fact, in all photolyases studied, the molecular conformations with the largest electronic couplings between the enzyme cofactor and DNA show the presence of adenine in 10-20% of the strongest-coupling tunneling pathways between the atoms of the electron donor and acceptor. Our theoretical analysis finds that adenine serves the critical role of fine-tuning rather than maximizing the donor-acceptor coupling within the range appropriate for the repair function.
