Direct observation of thymine dimer repair in DNA by photolyase
- †Departments of Physics, Chemistry, and Biochemistry, Programs of Biophysics, Chemical Physics, and Biochemistry, Ohio State University, 174 West 18th Avenue, Columbus, OH 43210; and §Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Mary Ellen Johns Building, CB 7260, Chapel Hill, NC 27599
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Contributed by Aziz Sancar, August 2, 2005
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.
Footnotes
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↵ ¶ To whom correspondence may be addressed. E-mail: aziz_sancar{at}med.unc.edu or dongping{at}mps.ohio-state.edu.
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↵ ‡ Y.-T.K. and C.S. contributed equally to this work.
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Author contributions: A.S. and D.Z. designed research and wrote the paper; and Y.-T.K., C.S., L.W., A.S., and D.Z. performed research and analyzed data.
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This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected on May 3, 2005.
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Abbreviations: Pyr<>Pyr, cyclobutane pyrimidine dimer; T<>T, cyclobutane thymine dimer.
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See accompanying Profile on page 16125.
- Copyright © 2005, The National Academy of Sciences
