Yamada Daichi, Kadono Ai, Maeno Tatsumi, Sato Wataru, Yanagisawa Sachiko, Hamamura Toshihiko, Shigeta Yasuteru, Yamamoto Junpei, Kubo Minoru
Department of Life Science, Graduate School of Science, University of Hyogo, Ako, Hyogo, Japan.
Division of Chemistry, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka, Japan.
Commun Chem. 2025 Aug 29;8(1):256. doi: 10.1038/s42004-025-01625-9.
Ultraviolet (UV) irradiation of DNA causes genotoxic photolesions, such as carcinogenic pyrimidine(6-4)pyrimidone photoproducts ((6-4)PPs). In many organisms, (6-4)PPs are repaired by (6-4) photolyases, which contain a flavin chromophore and use blue light energy to initiate the catalytic reaction. Although (6-4)PP repair has been shown to require the input of two successive photons, details of the mechanism remain elusive. Here, we applied recently developed time-resolved UV and infrared (IR) spectroscopic techniques to capture a key intermediate that awaits the second photon in the repair reaction of Xenopus laevis (6-4) photolyase. The results indicate that the intermediate is formed within 500 μs following the initial absorption of a photon and contains a four-membered oxetane ring that bridges two adjacent pyrimidine bases. These findings shed light on the molecular basis of DNA repair involving two-photon activation.
DNA的紫外线（UV）照射会导致基因毒性光损伤，如致癌的嘧啶（6-4）嘧啶酮光产物（（6-4）PPs）。在许多生物体中，（6-4）PPs由（6-4）光解酶修复，该酶含有黄素发色团并利用蓝光能量启动催化反应。尽管已表明（6-4）PP修复需要两个连续光子的输入，但其机制细节仍不清楚。在这里，我们应用最近开发的时间分辨紫外和红外（IR）光谱技术，捕获了非洲爪蟾（6-4）光解酶修复反应中等待第二个光子的关键中间体。结果表明，该中间体在最初吸收光子后的500微秒内形成，并且含有一个连接两个相邻嘧啶碱基的四元氧杂环丁烷环。这些发现揭示了涉及双光子激活的DNA修复的分子基础。
