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DNA repair

The cyclobutane dimer is formed between adjacent thymine nucleotides after ultraviolent damage, and due to the importance of their timely removal, there are several established repair mechanisms existing across species. It is unknown if nucleotide-based repair mechanisms can occur in nature, and not fully understood how the repair enzyme photolyase functions.

Overview

Electron movement involved in the repair of the cyclobutane dimer cannot be modelled without considering quantum mechanics. A nucleotide-based repair mechanism would require long-lasting excited states [1,2], whilst the transfer mechanism from the catalytic cofactor of photolyase could be explained as: quantum tunnelling, super-exchange, hopping, and proton-coupled electron transfer through water wire. The latter is known to depend on the wavelength of absorbed light, photolyase species and temperature of the enzyme [3-7].

Research team

Jim Al-Khalili profile image

Professor Jim Al-Khalili

Distinguished Chair, Professor of Physics, Professor of Public Engagement in Science, Centre Director

Brendan Howlin profile image

Professor Brendan Howlin

Professor of Computational Chemistry

Marco Sacchi profile image

Dr Marco Sacchi

Royal Society University Research Fellow, Principal Research Fellow in Physical and Computational Chemistry, Theme Leader in Sustainable Energy and Materials Research

References

[1] Bucher, D., Kufner, C., Schlueter, A., Carell, T., & Zinth, W. (2016, 1 13). UV-Induced Charge Transfer States in DNA Promote Sequence Selective Self-Repair. Journal of the American Chemical Society, 138(1), 186-190.

[2] Nguyen, K., & Burrows, C. (2011, 9 21). A prebiotic role for 8-oxoguanosine as a flavin mimic in pyrimidine dimer photorepair. Journal of the American Chemical Society, 133(37), 14586-14589.

[3]   Liu, Z., Tan, C., Guo, X., Kao, Y., Li, J., Wang, L., Sancar, A., Zhong, D. (2011). Dynamics and mechanism of cyclobutane pyrimidine dimer repair by DNA photolyase. Biophysics and Computational Biology Chemistry, 108(36), 14831-14836.

[4]    Rousseau, B., Shafei, S., Migliore, A., Stanley, R., & Beratan, D. (2018, 2 28). Determinants of Photolyase's DNA Repair Mechanism in Mesophiles and Extremophiles. Journal of the American Chemical Society, 140(8), 2853-2861.

[5]    Lee, W., Kodali, G., Stanley, R., & Matsika, S. (2016). Coexistence of Different Electron-Transfer Mechanisms in the DNA Repair Process by Photolyase. Chemistry - A European Journal, 22(32), 11371-11381.

[6]    Liu, Z., Tan, C., Guo, X., Li, J., Wang, L., Sancar, A., & Zhong, D. (2013, 8 6). Determining complete electron flow in the cofactor photoreduction of oxidized photolyase. Proceedings of the National Academy of Sciences of the United States of America, 110(32), 12966-12971.

[7]  Wang, H., Chen, X., & Fang, W. (2014, 11 5). Excited-state proton coupled electron transfer between photolyase and the damaged DNA through water wire: A photo-repair mechanism. Physical Chemistry Chemical Physics, 16(46), 25432-25441

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