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

0501578 - BFÚ 2019 RIV DE eng J - Journal Article
Malina, Jaroslav - Brabec, Viktor
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.
ChemistrySelect. Roč. 3, č. 46 (2018), s. 13076-13080. ISSN 2365-6549. E-ISSN 2365-6549
R&D Projects: GA ČR GA17-09436S
Institutional support: RVO:68081707
Keywords : polymerase * damage * nucleoside * energetics
OECD category: Biochemistry and molecular biology
Impact factor: 1.716, year: 2018

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.
Permanent Link: http://hdl.handle.net/11104/0293580