title: Rates of chemical cleavage of DNA and RNA oligomers containing guanine oxidation products.
abstract: The nucleobase guanine in DNA (dG) and RNA (rG) has the lowest standard reduction potential of the bases, rendering it a major site of oxidative damage in these polymers. Mapping the sites at which oxidation occurs in an oligomer via chemical reagents utilizes hot piperidine for cleaving oxidized DNA and aniline (pH 4.5) for cleaving oxidized RNA. In the present studies, a series of time-dependent cleavages of DNA and RNA strands containing various guanine lesions were examined to determine the strand scission rate constants. The guanine base lesions 8-oxo-7,8-dihydroguanine (OG), spiroiminodihydantoin (Sp), 5-guanidinohydantoin (Gh), 2,2,4-triamino-2H-oxazol-5-one (Z), and 5-carboxamido-5-formamido-2-iminohydantoin (2Ih) were evaluated in piperidine-treated DNA and aniline-treated RNA. These data identified wide variability in the chemical lability of the lesions studied in both DNA and RNA. Further, the rate constants for cleaving lesions in RNA were generally found to be significantly smaller than for lesions in DNA. The OG nucleotides were poorly cleaved in DNA and RNA; Sp nucleotides were slowly cleaved in DNA and did not cleave significantly in RNA; Gh and Z nucleotides cleaved in both DNA and RNA at intermediate rates; and 2Ih oligonucleotides cleaved relatively quickly in both DNA and RNA. The data are compared and contrasted with respect to future experimental design.
authors: Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors: Aaron M
authors: AM
authors: Fleming
authors: Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors: Omar
authors: O
authors: Alshykhly
authors: Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors: Judy
authors: J
authors: Zhu
authors: Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors: James G
authors: JG
authors: Muller
authors: Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors: Cynthia J
authors: CJ
authors: Burrows
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D053837:DNA Cleavage / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010880:Piperidines / Q000494:pharmacology; D012313:RNA / Q000737:chemistry*; D059367:RNA Cleavage / Q000187:drug effects; D013997:Time Factors
chemical_list: D000814:Aniline Compounds; D010880:Piperidines; D006147:Guanine; D012313:RNA; C032727:piperidine; D004247:DNA; C023650:aniline