ИСТИНА

Absorption of UV photons by DNA leads to formation of photodimes between the adjacent pyrimidine bases which detrimental for DNA biological function. In some organisms these photodimers are inverted by enzymes photolyases operating via photoinduced electron transfer. A photoexcited flavin cofactor of photolyases serves an electron donor to the photodimes. The quantum yield of the repair reaction is determined by competing forward and backward electron transfer reactions. Studies of photolyases [1] are focused on identifying electron transfer pathways that control the repair quantum yield. Determination of the photolyase 3D structure initiated computational investigations of the DNA repair reactions. One issue to be addressed by computational studies is evaluation of electron transfer rates to facilitate comparison with experimental findings. We apply multireference quantum-chemistry calculations for characterizing electron transfer between the flavin cofactor and DNA lesion (see Figure). In particular, the maximal electron transfer rates are estimated from excited state calculations with the help of the generalized Mulliken-Hush scheme. The obtained maximal rates map the most probable electron transfer pathways leading to one-electron reduction of the photodimer. Based on the estimated rates some electron-transfer pathways previously suggested in literature [1] are ruled out. The analysis of maximal rates establishes the role of energy tuning for increasing the repair quantum yield. The obtained results pave the way to evaluating controversial proposals and to eventually establishing the mechanism of photoinduced DNA repair by combining the computational and experimental results. The work is supported by the Russian Science Foundation grant no. 22-23-00418. [1] Yamamoto J., Plaza P. and Brettel K. (2017). Photochem. Photobiol., 93(1):51-66. https://lk.challenges2024.ru/n.php?n=3#current