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Backbone Conformational Equilibrium in Mismatched DNA Correlates with Enzyme Activity.


ABSTRACT: T:G mismatches in mammals arise primarily from the deamination of methylated CpG sites or the incorporation of improper nucleotides. The process by which repair enzymes such as thymine DNA glycosylase (TDG) identify a canonical DNA base in the incorrect pairing context remains a mystery. However, the abundant contacts of the repair enzymes with the DNA backbone suggest a role for protein-phosphate interaction in the recognition and repair processes, where conformational properties may facilitate the proper interactions. We have previously used 31P NMR to investigate the energetics of DNA backbone BI-BII interconversion and the effect of a mismatch or lesion compared to canonical DNA and found stepwise differences in ΔG of 1-2 kcal/mol greater than equivalent steps in unmo

SUBMITTER: Westwood MN 

PROVIDER: S-EPMC10552547 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature