2014.3.18 Dynamics and Mechanism of Ultraviolet-damaged DNA Repair by Photolyase
Dongping Zhong, Ph.D. Robert Smith Professor, Dept of Physics Professor, Dept of Chemistry and Biochemistry The Ohio State University |
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Time：14:00pm, Mar.18, 2014
Address：Rm. 101, Old Chemistry Building, east Wing, 1rd floor, CQB
Abstract: Photolyase uses blue light to restore the major ultraviolet (UV)-induced DNA damage, the cyclobutane pyrimidine dimer (CPD) and (6-4) photoproduct (6-4PP), but the detailed repair mechanisms are not known. Here, we use femtosecond spectroscopy to show the entire mapping of repair evolution in real time by capturing all elementary reaction steps from initial reactants, to various intermediates and to final products. For example, we observed that the CPD splits in two sequential steps within 90 ps and the electron tunnels between the cofactor and substrate through a remarkable route with an intervening adenine. Various site-directed mutations reveal that the active-site residues are critical to achieving high repair efficiency through a unique electrostatic environment by optimizing the redox potentials and local flexibility, and thus balance all catalytic reactions to maximize enzyme activity. These key findings reveal the complete spatio-temporal molecular picture of CPD and 6-4PP repair by photolyase and elucidate the underlying molecular mechanisms and their repair photocycles.
Host：Luhua LAI
