Dynamics and mechanism of cyclobutane pyrimidine dimer repair by DNA photolyase

Zheyun Liu, Chuang Tan, Xunmin Guo, Ya-Ting Kao, Jiang Li, Lijuan Wang, Aziz Sancar*, Dongping Zhong

*Corresponding author for this work

研究成果: Article同行評審

110 引文 斯高帕斯(Scopus)

摘要

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 ps through a cyclic electron-transfer radical mechanism. However, the two fundamental processes, electron-tunneling pathways and cyclobutane ring splitting, were not resolved. Here, we use ultra-fast 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 reveals 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.

原文English
頁(從 - 到)14831-14836
頁數6
期刊Proceedings of the National Academy of Sciences of the United States of America
108
發行號36
DOIs
出版狀態Published - 6 九月 2011

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