Bypass of a hydrocarbon adduct in an oligonucleotide template mediated by mispairing adjacent to the adduct.
The action of DNA polymerase (Sequenase Version 2.0) on an oligonucleotide template containing a 7-bromomethyl-benz[a]anthracene-deoxyadenosine adduct flanked by thymidine residues was investigated. The polymerase incorporated deoxyadenosine or deoxyguanosine residues opposite the thymidine 3' to the adduct with similar efficiencies. Whereas the normal A.T base pair led to arrest of polymerase progression along the template, formation of the G.T mismatch allowed incorporation of thymidine opposite the adduct and further primer extension. This mispair-mediated bypass was also seen with AMV reverse transcriptase and may represent a novel mechanism for overcoming the replication block of a bulky carcinogen--DNA adduct.
Hruszkewycz
A M
AM
Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702-1201.
Dipple
A
A
D001483:Base Sequence; D001551:Benz(a)Anthracenes; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000494:pharmacology; D003839:Deoxyadenosines; D004586:Electrophoresis; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D012194:RNA-Directed DNA Polymerase / Q000494:pharmacology
D001551:Benz(a)Anthracenes; D003839:Deoxyadenosines; D009841:Oligonucleotides; C001903:7-bromomethylbenzanthracene; C034970:bacteriophage T7 induced DNA polymerase; D012194:RNA-Directed DNA Polymerase; D004259:DNA-Directed DNA Polymerase