title: Adenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen-purine linkage in the differential global genomic repair propensity.
abstract: Computational modeling is employed to provide a plausible structural explanation for the experimentally-observed differential global genome repair (GGR) propensity of the ALII-N(2)-dG and ALII-N(6)-dA DNA adducts of aristolochic acid II. Our modeling studies suggest that an intrinsic twist at the carcinogen-purine linkage of ALII-N(2)-dG induces lesion site structural perturbations and conformational heterogeneity of damaged DNA. These structural characteristics correlate with the relative repair propensities of AA-adducts, where GGR recognition occurs for ALII-N(2)-dG, but is evaded for intrinsically planar ALII-N(6)-dA that minimally distorts DNA and restricts the conformational flexibility of the damaged duplex. The present analysis on the ALII adduct model systems will inspire future experimental studies on these adducts, and thereby may extend the list of structural factors that directly correlate with the propensity for GGR recognition.
authors.affiliation: Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, Alberta, T1K 3M4, Canada.
authors.forename: Preetleen
authors.initials: P
authors.lastname: Kathuria
authors.affiliation: Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, Alberta, T1K 3M4, Canada.
authors.forename: Purshotam
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, Alberta, T1K 3M4, Canada stacey.wetmore@uleth.ca.
authors.forename: Stacey D
authors.initials: SD
authors.lastname: Wetmore
mesh_terms: D034341:Aristolochic Acids / Q000737:chemistry*; D002273:Carcinogens / Q000737:chemistry*; D003198:Computer Simulation; D018736:DNA Adducts / Q000737:chemistry*; D004249:DNA Damage; D004260:DNA Repair; D016678:Genome; D009690:Nucleic Acid Conformation
chemical_list: D034341:Aristolochic Acids; D002273:Carcinogens; D018736:DNA Adducts