Dynamics of Mismatched Base Pairs in DNA

Christopher R. Guest, Remo A. Hochstrasser, Lawrence C. Sowers, David P. Millar

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

The structural dynamics of mismatched base pairs in duplex DNA have been studied by time-resolved fluorescence anisotropy decay measurements on a series of duplex oligodeoxynucleotides of the general type d[CGG(AP)GGC]•d[GCCXCCG], where AP is the fluorescent adenine analogue 2-aminopurine and X = T, A, G, or C. The anisotropy decay is caused by internal rotations of AP within the duplex, which occur on the picosecond time scale, and by overall rotational diffusion of the duplex. The correlation time and angular range of internal rotation of AP vary among the series of AP•X mismatches, showing that the native DNA bases differ in their ability to influence the motion of AP. These differences are correlated with the strength of base-pairing interactions in the various AP•X mismatches. The interactions are strongest with X = T or C. The ability to discern differences in the strength of base-pairing interactions at a specific site in DNA by observing their effect on the dynamics of base motion is a novel aspect of the present study. The extent of AP stacking within the duplex is also determined in this study since it influences the excited-state quenching of AP. AP is thus shown to be extrahelical in the AP•G mismatch. The association state of the AP-containing oligodeoxynucleotide strand is determined from the temperature-dependent tumbling correlation time. An oligodeoxynucleotide triplex is formed with a particular base sequence in a pH-dependent manner.

Original languageEnglish (US)
Pages (from-to)3271-3279
Number of pages9
JournalBiochemistry
Volume30
Issue number13
DOIs
StatePublished - Apr 1 1991
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Guest, C. R., Hochstrasser, R. A., Sowers, L. C., & Millar, D. P. (1991). Dynamics of Mismatched Base Pairs in DNA. Biochemistry, 30(13), 3271-3279. https://doi.org/10.1021/bi00227a015