title: Direct observation of thymine dimer repair in DNA by photolyase.
abstract: Photolyase uses light energy to split UV-induced cyclobutane dimers in damaged DNA, but its molecular mechanism has never been directly revealed. Here, we report the direct mapping of catalytic processes through femtosecond synchronization of the enzymatic dynamics with the repair function. We observed direct electron transfer from the excited flavin cofactor to the dimer in 170 ps and back electron transfer from the repaired thymines in 560 ps. Both reactions are strongly modulated by active-site solvation to achieve maximum repair efficiency. These results show that the photocycle of DNA repair by photolyase is through a radical mechanism and completed on subnanosecond time scale at the dynamic active site, with no net change in the redox state of the flavin cofactor.
authors.affiliation: Department of Physics, Ohio State University, 174 West 18th Avenue, Columbus, OH 43210, USA.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Kao
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Saxena
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Aziz
authors.initials: A
authors.lastname: Sancar
authors.forename: Dongping
authors.initials: D
authors.lastname: Zhong
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D004260:DNA Repair; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005609:Free Radicals; D011740:Pyrimidine Dimers / Q000378:metabolism*
chemical_list: D005609:Free Radicals; D011740:Pyrimidine Dimers; D005182:Flavin-Adenine Dinucleotide; D004255:Deoxyribodipyrimidine Photo-Lyase