通过光解酶直接观察DNA中胸腺嘧啶二聚体的修复
Direct observation of thymine dimer repair in DNA by photolyase.
作者信息
Kao Ya-Ting, Saxena Chaitanya, Wang Lijuan, Sancar Aziz, Zhong Dongping
机构信息
Department of Physics, Ohio State University, 174 West 18th Avenue, Columbus, OH 43210, USA.
出版信息
Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16128-32. doi: 10.1073/pnas.0506586102. Epub 2005 Sep 16.
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.
摘要
光解酶利用光能裂解受损DNA中紫外线诱导形成的环丁烷二聚体，但其分子机制从未被直接揭示。在此，我们报告通过将酶促动力学与修复功能进行飞秒同步来直接绘制催化过程。我们观察到在170皮秒内从激发态黄素辅因子到二聚体的直接电子转移，以及在560皮秒内从修复后的胸腺嘧啶的反向电子转移。这两个反应都受到活性位点溶剂化的强烈调节，以实现最大修复效率。这些结果表明，光解酶修复DNA的光循环是通过自由基机制进行的，并且在动态活性位点上在亚纳秒时间尺度内完成，黄素辅因子的氧化还原状态没有净变化。
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本文引用的文献
1
Femtosecond dynamics of flavin cofactor in DNA photolyase: radical reduction, local solvation, and charge recombination.DNA光解酶中黄素辅因子的飞秒动力学：自由基还原、局部溶剂化和电荷复合。
J Phys Chem B. 2005 Feb 3;109(4):1329-33. doi: 10.1021/jp044652b.
2
Crystal structure of a photolyase bound to a CPD-like DNA lesion after in situ repair.原位修复后与类CPD DNA损伤结合的光解酶的晶体结构。
Science. 2004 Dec 3;306(5702):1789-93. doi: 10.1126/science.1101598.
3
Dynamics of water in biological recognition.生物识别中的水动力学
Chem Rev. 2004 Apr;104(4):2099-123. doi: 10.1021/cr020689l.
4
On the nature of thymine photo-product.关于胸腺嘧啶光产物的性质。
Biochim Biophys Acta. 1961 Aug 5;51:332-9. doi: 10.1016/0006-3002(61)90174-3.
5
Photoreactivation in vitro of ultraviolet-inactivated Hemophilus influenzae transforming factor.紫外线灭活的流感嗜血杆菌转化因子的体外光复活作用
J Gen Physiol. 1958 Jan 20;41(3):451-71. doi: 10.1085/jgp.41.3.451.
6
Cis-syn thymidine dimer repair by DNA photolyase in real time.DNA光解酶实时修复顺式胸腺嘧啶二聚体。
Biochemistry. 2003 Jul 22;42(28):8558-68. doi: 10.1021/bi034015w.
7
Structure and function of DNA photolyase and cryptochrome blue-light photoreceptors.DNA光解酶和隐花色素蓝光光感受器的结构与功能
Chem Rev. 2003 Jun;103(6):2203-37. doi: 10.1021/cr0204348.
8
Crystal structure of thermostable DNA photolyase: pyrimidine-dimer recognition mechanism.耐热性DNA光解酶的晶体结构：嘧啶二聚体识别机制
Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13560-5. doi: 10.1073/pnas.241371398. Epub 2001 Nov 13.
9
Crystal structure of DNA photolyase from Anacystis nidulans.来自集胞藻的DNA光解酶的晶体结构。
Nat Struct Biol. 1997 Nov;4(11):887-91. doi: 10.1038/nsb1197-887.
10
Sunlight and the onset of skin cancer.阳光与皮肤癌的发病
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