title: Bifurcating electron-transfer pathways in DNA photolyases determine the repair quantum yield.
abstract: Photolyase is a blue-light-activated enzyme that repairs ultraviolet-induced DNA damage that occurs in the form of cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts. Previous studies on microbial photolyases have revealed an electron-tunneling pathway that is critical for the repair mechanism. In this study, we used femtosecond spectroscopy to deconvolute seven electron-transfer reactions in 10 elementary steps in all classes of CPD photolyases. We report a unified electron-transfer pathway through a conserved structural configuration that bifurcates to favor direct tunneling in prokaryotes and a two-step hopping mechanism in eukaryotes. Both bifurcation routes are operative, but their relative contributions, dictated by the reduction potentials of the flavin cofactor and the substrate, determine the overall quantum yield of repair.
authors.affiliation: Department of Physics, Department of Chemistry and Biochemistry, and Programs of Biophysics, Chemical Physics, and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Physics, Department of Chemistry and Biochemistry, and Programs of Biophysics, Chemical Physics, and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Physics, Department of Chemistry and Biochemistry, and Programs of Biophysics, Chemical Physics, and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Shi
authors.initials: S
authors.lastname: Shu
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Aziz
authors.initials: A
authors.lastname: Sancar
authors.affiliation: Department of Physics, Department of Chemistry and Biochemistry, and Programs of Biophysics, Chemical Physics, and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. zhong.28@osu.edu.
authors.forename: Dongping
authors.initials: D
authors.lastname: Zhong
mesh_terms: D000595:Amino Acid Sequence; D003067:Coenzymes / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004260:DNA Repair; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000737:chemistry* / Q000145:classification; D004138:Dinitrocresols / Q000737:chemistry; D004579:Electron Transport; D004583:Electrons; D005057:Eukaryotic Cells / Q000201:enzymology; D010802:Phylogeny; D011487:Protein Conformation; D011740:Pyrimidine Dimers / Q000737:chemistry*; D011789:Quantum Theory; D013057:Spectrum Analysis / Q000379:methods; D013379:Substrate Specificity; D014466:Ultraviolet Rays
chemical_list: D003067:Coenzymes; D004138:Dinitrocresols; D011740:Pyrimidine Dimers; C024132:4,6-dinitro-o-cresol; D004247:DNA; D004255:Deoxyribodipyrimidine Photo-Lyase