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Dynamics and Mechanism of Ultraviolet-damaged DNA Repair by Photolyase

日期: 2014-03-10
生命科学联合中心学术报告
题目:Dynamics and Mechanism of Ultraviolet-damaged DNA Repair by Photolyase.
报告人:Dongping Zhong, Ph.D.
Robert Smith Professor, Dept of Physics
Professor, Dept of Chemistry and Biochemistry
The Ohio State University
时间:2014-3-18(周二),13:00-14:00pm
地点:北京大学老化学楼东配楼101报告厅
联系人:生命科学联合中心,来鲁华
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.
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