Repair of a Dimeric Azetidine Related to the Thymine-Cytosine (6-4) Photoproduct by Electron Transfer Photoreduction

Ana B Fraga-Timiraos; Virginie Lhiaubet-Vallet; Miguel A Miranda

doi:10.1002/anie.201601475

Repair of a Dimeric Azetidine Related to the Thymine-Cytosine (6-4) Photoproduct by Electron Transfer Photoreduction

Angew Chem Int Ed Engl. 2016 May 10;55(20):6037-40. doi: 10.1002/anie.201601475. Epub 2016 Apr 8.

Authors

Ana B Fraga-Timiraos¹, Virginie Lhiaubet-Vallet², Miguel A Miranda³

Affiliations

¹ Instituto Universitario Mixto de Tecnología Química (UPV-CSIC), Universitat Politècnica de València, Consejo Superior de Investigaciones Científicas, Avda de los Naranjos, s/n, 46022, Valencia, Spain.
² Instituto Universitario Mixto de Tecnología Química (UPV-CSIC), Universitat Politècnica de València, Consejo Superior de Investigaciones Científicas, Avda de los Naranjos, s/n, 46022, Valencia, Spain. lvirgini@itq.upv.es.
³ Instituto Universitario Mixto de Tecnología Química (UPV-CSIC), Universitat Politècnica de València, Consejo Superior de Investigaciones Científicas, Avda de los Naranjos, s/n, 46022, Valencia, Spain. mmiranda@qim.upv.es.

PMID: 27061458
DOI: 10.1002/anie.201601475

Abstract

Photolyases are intriguing enzymes that take advantage of sunlight to restore lesions like cyclobutane pyrimidine dimers or (6-4) photoproducts. This work focused on the photoreductive process responsible for splitting of the azetidine ring proposed to occur during (6-4) photoproduct repair at a thymine-cytosine sequence. A model compound formed by photocycloaddition between thymine and 6-azauracil has been designed to mimic the elusive azetidine intermediate. The photoinduced electron transfer process has been investigated by means of steady-state and time-resolved fluorescence using photosensitizers with oxidation potentials in the singlet excited state ranging from -3.3 to -2.1 V vs. SCE. Azetidine ring splitting and recovery of "repaired" bases were proven by HPLC analysis.

Keywords: 6-azauracil; DNA damage; cycloreversion; fluorescence; photosensitization.

Publication types

Research Support, Non-U.S. Gov't