Dynamics and Mechanism of Cyclobutane Pyrimidine Dimer Repair by DNA Photolyase

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 Aug 2

PMID 21804035

Citations 55

Authors

Zheyun Liu

Chuang Tan

Xunmin Guo

Ya-Ting Kao

Jiang Li

Lijuan Wang

Aziz Sancar

Dongping Zhong

Affiliations

Soon will be listed here.

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 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 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 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.

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References

Kim S, Hartman R, Rose S . Solvent dependence of pyrimidine dimer splitting in a covalently linked dimer-indole system. Photochem Photobiol. 1990; 52(4):789-94. DOI: 10.1111/j.1751-1097.1990.tb08683.x. View

Lima-Bessa K, Menck C . Skin cancer: lights on genome lesions. Curr Biol. 2005; 15(2):R58-61. DOI: 10.1016/j.cub.2004.12.056. View

Zhong D . Ultrafast catalytic processes in enzymes. Curr Opin Chem Biol. 2007; 11(2):174-81. DOI: 10.1016/j.cbpa.2007.02.034. View

Essen L, Klar T . Light-driven DNA repair by photolyases. Cell Mol Life Sci. 2006; 63(11):1266-77. PMC: 11136382. DOI: 10.1007/s00018-005-5447-y. View

Jorns M, Wang B, Jordan S, Chanderkar L . Chromophore function and interaction in Escherichia coli DNA photolyase: reconstitution of the apoenzyme with pterin and/or flavin derivatives. Biochemistry. 1990; 29(2):552-61. DOI: 10.1021/bi00454a032. View

Prytkova T, Beratan D, Skourtis S . Photoselected electron transfer pathways in DNA photolyase. Proc Natl Acad Sci U S A. 2007; 104(3):802-7. PMC: 1783394. DOI: 10.1073/pnas.0605319104. View

Wang H, Lin S, Allen J, Williams J, Blankert S, Laser C . Protein dynamics control the kinetics of initial electron transfer in photosynthesis. Science. 2007; 316(5825):747-50. DOI: 10.1126/science.1140030. View

Chang C, Guo L, Kao Y, Li J, Tan C, Li T . Ultrafast solvation dynamics at binding and active sites of photolyases. Proc Natl Acad Sci U S A. 2010; 107(7):2914-9. PMC: 2840346. DOI: 10.1073/pnas.1000001107. View

Li J, Liu Z, Tan C, Guo X, Wang L, Sancar A . Dynamics and mechanism of repair of ultraviolet-induced (6-4) photoproduct by photolyase. Nature. 2010; 466(7308):887-890. PMC: 3018752. DOI: 10.1038/nature09192. View

10.

Kao Y, Saxena C, Wang L, Sancar A, Zhong D . Femtochemistry in enzyme catalysis: DNA photolyase. Cell Biochem Biophys. 2007; 48(1):32-44. DOI: 10.1007/s12013-007-0034-5. View

11.

Sancar A . Structure and function of DNA photolyase and cryptochrome blue-light photoreceptors. Chem Rev. 2003; 103(6):2203-37. DOI: 10.1021/cr0204348. View

12.

Hassanali A, Zhong D, Singer S . An AIMD study of CPD repair mechanism in water: role of solvent in ring splitting. J Phys Chem B. 2011; 115(14):3860-71. PMC: 3099306. DOI: 10.1021/jp107723w. View

13.

Heelis P, Payne G, Sancar A . Photochemical properties of Escherichia coli DNA photolyase: selective photodecomposition of the second chromophore. Biochemistry. 1987; 26(15):4634-40. DOI: 10.1021/bi00389a007. View

14.

Kao Y, Tan C, Song S, Ozturk N, Li J, Wang L . Ultrafast dynamics and anionic active states of the flavin cofactor in cryptochrome and photolyase. J Am Chem Soc. 2008; 130(24):7695-701. PMC: 2661107. DOI: 10.1021/ja801152h. View

15.

Mees A, Klar T, Gnau P, Hennecke U, Eker A, Carell T . Crystal structure of a photolyase bound to a CPD-like DNA lesion after in situ repair. Science. 2004; 306(5702):1789-93. DOI: 10.1126/science.1101598. View

16.

Hassanali A, Zhong D, Singer S . An AIMD study of the CPD repair mechanism in water: reaction free energy surface and mechanistic implications. J Phys Chem B. 2011; 115(14):3848-59. PMC: 3100802. DOI: 10.1021/jp107722z. View

17.

Maul M, Barends T, Glas A, Cryle M, Domratcheva T, Schneider S . Crystal structure and mechanism of a DNA (6-4) photolyase. Angew Chem Int Ed Engl. 2008; 47(52):10076-80. DOI: 10.1002/anie.200804268. View

18.

Gray H, Winkler J . Electron transfer in proteins. Annu Rev Biochem. 1996; 65:537-61. DOI: 10.1146/annurev.bi.65.070196.002541. View

19.

Daya-Grosjean L, Dumaz N, Sarasin A . The specificity of p53 mutation spectra in sunlight induced human cancers. J Photochem Photobiol B. 1995; 28(2):115-24. DOI: 10.1016/1011-1344(95)07130-t. View

20.

Sancar A, Smith F, Sancar G . Purification of Escherichia coli DNA photolyase. J Biol Chem. 1984; 259(9):6028-32. View