Premium
Probing the Thermodynamics of Incorporation of N 6 ‐methyl‐dATP Opposite an Abasic Site, dCMP, and dTMP During Simulated DNA Synthesis by Differential Scanning Calorimetry
Author(s) -
Malina Jaroslav,
Brabec Viktor
Publication year - 2018
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803565
Subject(s) - ap site , differential scanning calorimetry , dna , dna polymerase , chemistry , nucleotide , biophysics , stereochemistry , microbiology and biotechnology , dna damage , biochemistry , biology , physics , thermodynamics , gene
Previous reports indicated that when an abasic (apurinic/apyrimidinic, AP) site is bypassed by DNA polymerases, dATP is preferentially inserted. Here we evaluate, using differential scanning calorimetry, the thermodynamic changes associated with incorporation of N 6 ‐methyl‐dATP opposite an AP site, dCMP, and dTMP during simulated DNA polymerization. The results confirm that AP sites block DNA polymerases one nucleotide prior to the lesion. Thermodynamic data imply that the propensity of N 6 ‐methyl‐dAMP for elongation, when incorporated opposite an AP site, is higher than that of dAMP in agreement with a higher promutagenic potential of N 6 ‐methyl‐dATP if placed opposite a non‐instructional DNA lesion, such as an AP site.