A (6-4) Photolyase Model: Repair of DNA (6-4) Lesions Requires a Reduced and Deprotonated Flavin This work was supported by the Volkswagen Foundation, the Fonds der Chemischen Industry, and the Bundesministerium für Bildung und Forschung (BMBF: Neue Medien in der Bildung).

Abstract

Photolyase‐catalyzed repair of pyrimidine (6‐4) photoadducts was modeled with synthetic, covalently linked flavin–oxetane 1. The repair reaction (oxetane splitting) requires the reduced flavin in its deprotonated form. The key step of the repair reaction involves an electron transfer from the flavin to the oxetane.

Model studies of the (6–4) photoproduct photoreactivation: efficient photosensitized splitting of thymine oxetane units by covalently linked tryptophan in high polarity solvents

“…6- 8 The strongest support for the ET model came from the investigation of photoinduced cleavage of an oxetane ring covalently linked to flavin. 7 In this model system, it was found that only two-electron-reduced and deprotonated flavin induced more efficient photosplitting of the oxetane ring. This result further demonstrated the close mechanistic similarities between CPD photolyase and (6-4) photolyase.…”

“…15 The result is well in agreement with the observation from a covalently linked flavin-oxetane system, i.e., the quantum yield of the flavin-oxetane system was 0.023, and 0.01 for a flavin-CPD system. 7 The two-fold higher splitting quantum yield of the oxetane system than the CPD system can be explained by the splitting rate of the oxetane anion radical (>10 7 s −1 ) 6b being faster than that of the CPD radical anion (∼10 6 s −1 ). 20 A fast splitting of the oxetane radical anion can efficiently compete with BET within the zwitterionic intermediate.…”

Nonradiative decay of photoexcited methylated guanine

“…4 shows the fewest switches probability, eqn. (7), for a hop from the S 1 excited state to the S 0 ground state as a function of simulation time after vertical excitation at time t ¼ 0. As these two representative trajectories illustrate, nonadiabatic coupling is quite similar for both tautomers during the first approximately 40 fs.…”

“…Ultraviolet radiation poses, in this respect, a serious threat to the well-ordered sequence of hydrogen-bonded DNA base pairs. [5][6][7][8] It is generally believed that, for this reason, excited state lifetimes of nucleobases are short in order to minimize the potential for radiation induced damage. [8][9][10] Recent experimental [11][12][13][14][15] and theoretical studies 16,17 have shown that there are large variations in the photophysical properties of different guanine tautomers.…”

Similarities and Differences between Cyclobutane Pyrimidine Dimer Photolyase and (6-4) Photolyase as Revealed by Resonance Raman Spectroscopy

“…Similar association constants of ϳ10 Ϫ9 M were identified for CPD and the photoproduct in the complex of the corresponding photolyase, respectively, whereas those for the undamaged DNA were Ͼ4 orders of magnitude lower or not detectable (4 -6). Both photolyases contain FAD as an essential catalytic cofactor (7,8). The amino acid sequences of (6-4) and CPD photolyases, especially within the FAD-binding region, are closely related, suggesting that these two enzymes share similar structure and reaction mechanisms (9); however, the quantum yield for photorecovery is significantly lower for (6-4) photolyase than for CPD photolyase (4,6,10).…”