title: Tolerance of base pair size and shape in postlesion DNA synthesis.
abstract: The influence of base pair size and shape on the fidelity of DNA polymerase-mediated extension past lesion-containing mispairs was examined. Primer extension analysis was performed with synthetic nucleosides paired opposite the pro-mutagenic DNA lesion O(6)-benzylguanine (O(6)-BnG). These data indicate that the error-prone DNA polymerase IV (Dpo4) inefficiently extended past the larger Peri:O(6)-BnG base pair, and in contrast, error-free extension was observed for the smaller BIM:O(6)-BnG base pair. Steady-state kinetic analysis revealed that Dpo4 catalytic efficiency was strongly influenced by the primer:template base pair. Compared to the C:G pair, a 1.9- and 79,000-fold reduction in Dpo4 efficiency was observed for terminal C:O(6)-BnG and BIM:G base pairs respectively. These results demonstrate the impact of geometrical size and shape on polymerase-mediated mispair extension.
authors.affiliation: Department of Health Sciences and Technology, Institute of Food Nutrition and Health, ETH Zürich, Schmelzbergstrasse 9, 8092 Zürich, Switzerland.
authors.forename: Hailey L
authors.initials: HL
authors.lastname: Gahlon
authors.forename: W Bernd
authors.initials: WB
authors.lastname: Schweizer
authors.forename: Shana J
authors.initials: SJ
authors.lastname: Sturla
mesh_terms: D020137:Base Pair Mismatch; D020029:Base Pairing; D002384:Catalysis; D018736:DNA Adducts; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000737:chemistry; D017931:DNA Primers; D004261:DNA Replication / Q000235:genetics / Q000502:physiology*; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry; D006160:Guanosine Triphosphate / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D048229:Sulfolobus solfataricus; D013824:Thermus / Q000201:enzymology
chemical_list: D018736:DNA Adducts; D017931:DNA Primers; C064976:O(6)-benzylguanine; D006147:Guanine; D006160:Guanosine Triphosphate; D019951:DNA Polymerase beta