Indications of 5′ to 3′ Interbase Electron Transfer as the First Step of Pyrimidine Dimer Formation Probed by a Dinucleotide Analog

5 years ago

Indications of 5′ to 3′ Interbase Electron Transfer as the First Step of Pyrimidine Dimer Formation Probed by a Dinucleotide Analog

Degang Liu, Surya Adhikari, Yajun Jian, Egle Maximowitsch, Tatiana Domratcheva, Lei Li

Pyrimidine dimers are the most common DNA lesions generated under UV radiation. To reveal the molecular mechanisms behind their formation, it is of significance to reveal the roles of each pyrimidine residue. We thus replaced the 5′-pyrimidine residue with a photochemically inert xylene moiety (X). The electron-rich X can be readily oxidized but not reduced, defining the direction of interbase electron transfer (ET). Irradiation of the XpT dinucleotide under 254 nm UV light generates two major photoproducts: a pyrimidine (6-4) pyrimidone analog (6-4PP) and an analog of the so-called spore photoproduct (SP). Both products are formed by reaction at C4=O of the photo-excited 3′-thymidine (T), which indicates that excitation of a single “driver” residue is sufficient to trigger pyrimidine dimerization. Our quantum-chemical calculations demonstrated that photo-excited 3′-T accepts an electron from 5′-X. The resulting charge-separated radical pair lowers its energy upon formation of interbase covalent bonds, eventually yielding 6-4PP and SP. Pyrimidine dimer formation: Pyrimidine dimers are the most common DNA lesions generated under UV radiation. To reveal the molecular mechanisms behind their formation, the 5′-pyrimidine residue was replaced with a photochemically inert xylene moiety (X), which can be readily oxidized but not reduced, defining the direction of interbase electron transfer (ET).

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201700045