Browsing by Subject "pyrimidine dimers"

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    Indications of 5′ to 3′ Interbase Electron Transfer as the First Step of Pyrimidine Dimer Formation Probed by a Dinucleotide Analog
    (Wiley, 2017-06) Jian, Yajun; Maximowitsch, Egle; Adhikari, Surya; Li, Lei; Domratcheva, Tatiana; Chemistry and Chemical Biology, School of Science
    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.
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    Using Organic Synthesis and Chemical Analysis to Understand the Photochemistry of Spore Photoproduct and Other Pyrimidine Dimers
    (Thieme, 2018) Li, Lei; Chemistry and Chemical Biology, School of Science
    Pyrimidine dimerization is the dominant DNA photoreaction occurring in vitro and in vivo. Three types of dimers, cyclobutane pyrimidine dimers (CPDs), pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), and the spore photoproduct (SP), are formed from the direct dimerization process; it is of significance to understand the photochemistry and photobiology of these dimers. Traditionally, pyrimidine dimerization was studied by using the natural pyrimidine residues thymine and cytosine, which share similar chemical structures and similar reactivity, making it sometimes less straightforward for one to identify the key pyrimidine residue that needs to be excited to trigger the photoreaction. We thus adopted synthetic chemistry to selectively modify the pyrimidine residues or to introduce pyrimidine analogs to the selected positions before UV irradiation is applied. By monitoring the subsequent outcomes from the photoreaction, we were able to gain unique mechanistic insights into the photochemistry of SP as well as of CPDs and 6-4PPs. Moreover, our approaches have resulted in several useful “tools” that can facilitate the understanding of lesion photobiology. Our results summarized in this account illustrate what organic synthesis/chemical analysis may allow us to achieve in future DNA lesion biology studies.