Effects of sequence contexts on misincorporation of nucleotides opposite 2‐hydroxyadenine

Abstract

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 α and β 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.