Dynamics and mechanism of cyclobutane pyrimidine dimer repair by DNA photolyase

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Title: Dynamics and mechanism of cyclobutane pyrimidine dimer repair by DNA photolyase
Creators: Liu, Zheyun
Advisor: Zhong, Dongping
Issue Date: 2012-02
Abstract: Photolyase uses blue light to restore the major ultraviolet (UV)-induced DNA damage, the cyclobutane pyrimidine dimer (CPD), to two normal bases by splitting the cyclobutane ring. Our earlier studies showed that the overall repair is completed in 700 picoseconds (ps) through a cyclic electron-transfer (ET) radical mechanism. However, the two fundamental processes, electron tunneling pathways and cyclobutane ring splitting, were not resolved. Here, we use ultrafast UV absorption spectroscopy to show 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. Site-directed mutagenesis reveal that the active-site residues are critical to achieving high repair efficiency, a unique electrostatic environment to optimize 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 repair by photolyase and elucidate the underlying molecular mechanism of the enzyme’s high repair efficiency.
Citation: Z. Liu, C. Tan, X. Guo, Y.-T. Kao, J. Li, L. Wang, A. Sancar, and D. Zhong, Proc. Natl. Acad. Sci. USA 108, 14831 (2011)
Embargo: No embargo
Series/Report no.: 2012 Edward F. Hayes Graduate Research Forum. 26th
Keywords: DNA repair
ultrafast enzyme dynamics
thymine dimer splitting
electron tunneling pathway
active-site mutation
Description: Mathematical and Physical Sciences: 2nd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
URI: http://hdl.handle.net/1811/51689
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