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<p>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 <i>Xenopus laevis</i> (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.</p>

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Infrared and ultraviolet spectroscopic characterization of a key intermediate during DNA repair by (6-4) photolyase

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月29日

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  • Daichi Yamada,
  • Ai Kadono,
  • Tatsumi Maeno,
  • Wataru Sato,
  • Sachiko Yanagisawa,
  • Toshihiko Hamamura,
  • Yasuteru Shigeta,
  • Junpei Yamamoto,
  • Minoru Kubo

摘要

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.