We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Thermodynamic Impact of Abasic Sites on Simulated Translesion DNA Synthesis.
- Authors
Malina, Jaroslav; Brabec, Viktor
- Abstract
Loss of a base in DNA and the creation of an abasic (apurinic/apyrimidinic, AP) site is a frequent lesion that may occur spontaneously, or as a consequence of the action of DNA-damaging agents. The AP lesion is mutagenic or lethal if not repaired. We report a systematic thermodynamic investigation by differential scanning calorimetry on the evolution, during primer extension, of a model AP site in chemically simulated DNA translesion synthesis. Incorporation of dAMP (deoxyadenosine monophosphate), as well as dTMP (deoxythymidine monophosphate), opposite an AP site is enthalpically unfavorable, although incorporation of dTMP is more enthalpically unfavorable than that of dAMP. This finding is in a good agreement with experimental data showing that AP sites block various DNA polymerases of eukaryotic and prokaryotic origin and that, if bypassed, dAMP is preferentially inserted, whereas insertion of dTMP is less likely. The results emphasize the importance of thermodynamic contributions to the insertion of nucleotides opposite an AP site by DNA polymerases.
- Subjects
DNA synthesis; APURINIC acid; DNA damage; DNA polymerases; DIFFERENTIAL scanning calorimetry
- Publication
Chemistry - A European Journal, 2014, Vol 20, Issue 25, p7566
- ISSN
0947-6539
- Publication type
Article
- DOI
10.1002/chem.201402600