Effect of sequence contexts on misincorporation of nucleotides opposite 2-hydroxyadenine.
Twelve oligonucleotides containing 2-hydroxyadenine (2-OH-Ade) with different neighboring bases were used as templates in DNA polymerase reactions,and the effects of the sequence contexts were investigated. DNA polymerases alpha and beta inserted dTMP and dCMP opposite 2-OH-Ade in most of the oligonucleotides tested. The Klenow fragment of DNA polymerase I primarily incorporated dTMP and dGMP. Effects of the 5'-flanking base of 2-OH-Ade was found when the 3'-flanking base of 2-OH-Ade was A or C. Incorporation of dAMP occurred when the oxidized base was located in a 5' -TA*A- 3' (A* represents 2-OH-Ade) sequence. These results suggest that the formation of 2-OH-Ade in DNA may induce all the mutations involving A (A-->G transition, and A-->T and A-->C transversions) in cells.
Kamiya
H
H
Department of Environmental Oncology, University of Occupational and Environmental Health, Kitakyushi, Japan.
Kasai
H
H
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002417:Cattle; D004256:DNA Polymerase I / Q000378:metabolism*; D004257:DNA Polymerase II / Q000378:metabolism*; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D006147:Guanine; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013698:Templates, Genetic; D013938:Thymidine Monophosphate / Q000378:metabolism; D013950:Thymus Gland / Q000201:enzymology
D003848:Deoxyguanine Nucleotides; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D013938:Thymidine Monophosphate; D006147:Guanine; C007257:2'-deoxyguanosine 5'-phosphate; C008183:isoguanine; D004256:DNA Polymerase I; D004257:DNA Polymerase II