Thermodynamic stability of base pairs, between 2-hydroxyadenine and incoming nucleotides as a determinant of nucleotide incorporation specificity during replication
J. Kawakami et al., Thermodynamic stability of base pairs, between 2-hydroxyadenine and incoming nucleotides as a determinant of nucleotide incorporation specificity during replication, NUCL ACID R, 29(16), 2001, pp. 3289-3296
We investigated the thermodynamic stability of double-stranded DNAs with an
oxidative DNA lesion, 2-hydroxyadenine (2-OH-Ade), in two different sequen
ce contexts (5'-GA*C-3' and 5'-TA*A-3, A* represents 2-OH-Ade). When an A*-
N pair (N, any nucleotide base) was located in the center of a duplex, the
thermodynamic stabilities of the duplexes were similar for all the natural
bases except A (N = T, C and G). On the other hand, for the duplexes with t
he A*-N pair at the end, which mimic the nucleotide incorporation step, the
stabilities of the duplexes were dependent on their sequence. The order of
stability is T > G > C >> A in the 5'-GA*C-3' sequences and T > A > C > G
in the 5'-TA*A-3' sequences. Because T/G/C and T/A are nucleotides, incorpo
rated opposite to 2-OH-Ade in the 5-GA*C-3' and 5'-A*A-3' sequences, respec
tively, these results agree with the tendency of mutagenic misincorporation
of the nucleotides opposite to 2-OH-Ade in vitro. Thus, the thermodynamic
stability of the A*-N base pair may be an important factor for the mutation
spectra of 2-OH-Ade.