Issue 31, 2020

Melting temperature measurement and mesoscopic evaluation of single, double and triple DNA mismatches

Abstract

Unlike the canonical base pairs AT and GC, the molecular properties of mismatches such as hydrogen bonding and stacking interactions are strongly dependent on the identity of the neighbouring base pairs. As a result, due to the sheer number of possible combinations of mismatches and flanking base pairs, only a fraction of these have been studied in varying experiments or theoretical models. Here, we report on the melting temperature measurement and mesoscopic analysis of contiguous DNA mismatches in nearest-neighbours and next-nearest neighbour contexts. A total of 4032 different mismatch combinations, including single, double and triple mismatches were covered. These were compared with 64 sequences containing all combinations of canonical base pairs in the same location under the same conditions. For a substantial number of single mismatch configurations, 15%, the measured melting temperatures were higher than the least stable AT base pair. The mesoscopic calculation, using the Peyrard–Bishop model, was performed on the set of 4096 sequences, and resulted in estimates of on-site and nearest-neighbour interactions that can be correlated to hydrogen bonding and base stacking. Our results confirm many of the known properties of mismatches, including the peculiar sheared stacking of tandem GA mismatches. More intriguingly, it also reveals that a number of mismatches present strong hydrogen bonding when flanked on both sites by other mismatches. To highlight the applicability of our results, we discuss a number of practical situations such as enzyme binding affinities, thymine DNA glycosylase repair activity, and trinucleotide repeat expansions.

Graphical abstract: Melting temperature measurement and mesoscopic evaluation of single, double and triple DNA mismatches

Supplementary files

Article information

Article type
Edge Article
Submitted
23 Mar 2020
Accepted
23 Jul 2020
First published
23 Jul 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2020,11, 8273-8287

Melting temperature measurement and mesoscopic evaluation of single, double and triple DNA mismatches

L. M. Oliveira, A. S. Long, T. Brown, K. R. Fox and G. Weber, Chem. Sci., 2020, 11, 8273 DOI: 10.1039/D0SC01700K

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