Faculty Publications

Mechanical Properties of Base-Modified DNA are Not Strictly Determined by Base Stacking or Electrostatic Interactions

Document Type

Article

Journal/Book/Conference Title

Biophysical Journal

Volume

107

Issue

2

First Page

448

Last Page

459

Abstract

This work probes the mystery of what balance of forces creates the extraordinary mechanical stiffness of DNA to bending and twisting. Here we explore the relationship between base stacking, functional group occupancy of the DNA minor and major grooves, and DNA mechanical properties. We study double-helical DNA molecules substituting either inosine for guanosine or 2,6-diaminopurine for adenine. These DNA variants, respectively, remove or add an amino group from the DNA minor groove, with corresponding changes in hydrogen-bonding and base stacking energy. Using the techniques of ligase-catalyzed cyclization kinetics, atomic force microscopy, and force spectroscopy with optical tweezers, we show that these DNA variants have bending persistence lengths within the range of values reported for sequence-dependent variation of the natural DNA bases. Comparison with seven additional DNA variants that modify the DNA major groove reveals that DNA bending stiffness is not correlated with base stacking energy or groove occupancy. Data from circular dichroism spectroscopy indicate that base analog substitution can alter DNA helical geometry, suggesting a complex relationship among base stacking, groove occupancy, helical structure, and DNA bend stiffness. © 2014 Biophysical Society.

Department

Department of Chemistry and Biochemistry

Original Publication Date

7-15-2014

DOI of published version

10.1016/j.bpj.2014.04.066

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