Browsing by Subject "DNA lesions"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    ROLE OF CHECKPOINT PROTEINS IN THE SUCCESS OF BIR
    (Office of the Vice Chancellor for Research, 2012-04-13) Vasan, Soumini; Deem, Angela; Argueso, Lucas; Malkova, Anna
    Break-induced replication (BIR) is an important homologous recombina-tion (HR) pathway employed to repair DNA lesions and has been implicated in various chromosomal instabilities, including loss of heterozygosity, trans-locations, and alternative telomere lengthening. Here, we study the role of checkpoint proteins in DNA repair in yeast Saccharomyces cerevisiae. Cell cycle checkpoints are required for the proper progression of the cell cycle. These checkpoint proteins sense problems during the cell cycle and halt pro-gression to allow mistakes to be corrected and the loss of checkpoint con-trols leads to major defects. RAD9 and RAD24, two important checkpoint proteins play a vital role in arresting the cell cycle upon DNA damage and are also responsible for bringing together the DNA repair machinery. We ob-served that mutations made in the genes encoding RAD9 and RAD24 result-ed in the formation of multiple sectors in individual colonies where, every in-dividual sector repaired differently. We analyze the frequency of different re-pair outcomes associated with BIR in these multi-sectored events. We also report that defective BIR in these checkpoint mutants lead to formation of half-crossovers similar to NRTs reported in mammals, which are implicated in the initiation of cascades of genomic instability characteristic of human cancer cells. 1Department of Environmental and Radiological Health Sciences, College of Veterinary Medi-cine & Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.