ULTRAFAST DNA DYNAMICS USING NOVEL PHOTOPHYSICAL PROBES

University Of South Carolina At Columbia, Columbia SC

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Abstract

DESCRIPTION: Fluctuations in the local structure of DNA make it a unique environment for biochemical reactions-duplex DNA is much more structured than a liquid, but significantly more dynamic than a solid. The variation of the lifetime and magnitude of these fluctuations with respect to sequence has been implicated in the unique functions of specific DNA sequences. Overall, structural fluctuations in DNA play a critical role in a variety of biological phenomena such as sequence recognition, transcriptional regulation, chromosome packaging, DNA damage and repair, and the misfunction of aberrant DNA structures. This project will make the first systematic measurements of the localized fluctuations of DNA structure on the picosecond and femtosecond time scales. These short time scales are the most important for environmental affects on biochemical reactions and for determining the local mechanical properties of DNA. This project will determine how localized motions of duplex DNA are affected by base-pair sequence, base-pair mismatches, mutagenic lesions, phosphate charge, counterion mobility, interstrand hydrogen bonding, interstrand cross-links, and sugar conformational changes. The approach to be used is a combination of two new ideas: 1) synthetic incorporation of novel fluorescent glycoside probes into oligonucleotides, including both dielectric and mechanical probes, and 2) adaptation of the technique of time-resolved Stokes-shift spectroscopy, which was originally developed for measuring solvation dynamics in liquids, to the study of ultrafast DNA dynamics.