Nanomechanics of Diaminopurine-Substituted DNA

Biophysical Journal
Matteo CristofaloFrancesco Mantegazza

Abstract

2,6-diaminopurine (DAP) is a nucleobase analog of adenine. When incorporated into double-stranded DNA (dsDNA), it forms three hydrogen bonds with thymine. Rare in nature, DAP substitution alters the physical characteristics of a DNA molecule without sacrificing sequence specificity. Here, we show that in addition to stabilizing double-strand hybridization, DAP substitution also changes the mechanical and conformational properties of dsDNA. Thermal melting experiments reveal that DAP substitution raises melting temperatures without diminishing sequence-dependent effects. Using a combination of atomic force microscopy (AFM), magnetic tweezer (MT) nanomechanical assays, and circular dichroism spectroscopy, we demonstrate that DAP substitution increases the flexural rigidity of dsDNA yet also facilitates conformational shifts, which manifest as changes in molecule length. DAP substitution increases both the static and dynamic persistence length of DNA (measured by AFM and MT, respectively). In the static case (AFM), in which tension is not applied to the molecule, the contour length of DAP-DNA appears shorter than wild-type (WT)-DNA; under tension (MT), they have similar dynamic contour lengths. At tensions above 60 pN, WT-DNA unde...Continue Reading

Citations

Nov 18, 2020·Biopolymers·Andrew Travers
Apr 14, 2021·Nucleic Acids Research·Enrico BuglioneFrancesco Mantegazza
May 1, 2021·Science·Michael W Grome, Farren J Isaacs
Jun 29, 2021·Physical Chemistry Chemical Physics : PCCP·Vinoth Sundar RajanL Marcus Wilhelmsson

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