title: C8-linked bulky guanosine DNA adducts: experimental and computational insights into adduct conformational preferences and resulting mutagenicity.
abstract: Bulky DNA adducts are formed through the covalent attachment of aryl groups to the DNA nucleobases. Many of these adducts are known to possess conformational heterogeneity, which is responsible for the variety of mutagenic outcomes associated with these lesions. The present contribution reviews several conformational and mutagenic themes that are prevalent among the DNA adducts formed at the C8-site of the guanine nucleobase. The most important conclusions obtained (to date) from experiments are summarized including the anti/syn conformational preference of the adducts, their potential to inflict DNA mutations and mismatch stabilization, and their interactions with DNA polymerases and repair enzymes. Additionally, the unique role that computer calculations can play in understanding the structural properties of these adducts are highlighted.
authors.affiliation: Department of Chemistry & Biochemistry, University of Lethbridge, Lethbridge, Alberta, Canada.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Millen
authors.forename: Purshotam
authors.initials: P
authors.lastname: Sharma
authors.forename: Stacey D
authors.initials: SD
authors.lastname: Wetmore
mesh_terms: D000588:Amines / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry*; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism; D004967:Estrogens / Q000737:chemistry; D006151:Guanosine / Q000737:chemistry*; D006834:Hydrazines / Q000737:chemistry; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010636:Phenols / Q000737:chemistry; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry
chemical_list: D000588:Amines; D018736:DNA Adducts; D004967:Estrogens; D006834:Hydrazines; D010636:Phenols; D011084:Polycyclic Aromatic Hydrocarbons; D006151:Guanosine; C029424:hydrazine; C042329:phenoxy radical; D004259:DNA-Directed DNA Polymerase; D045643:DNA Repair Enzymes