Dynamics of DNA conformations and DNA-protein interactions
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0899-N03-06.1
Dynamics of DNA conformations and DNA-protein interaction Ralf Metzler, Tobias Ambj¨ornsson, and Michael A. Lomholt NORDITA, Blegdamsvej 17, 2100 København Ø, Denmark Oleg Krichevsky Physics Department, Ben Gurion University, Be’er Sheva 84105, Israel ABSTRACT Optical tweezers, atomic force microscopes, patch clamping, or fluorescence techniques make it possible to study both the equilibrium conformations and dynamics of single DNA molecules as well as their interaction with binding proteins. In this paper we address the dynamics of local DNA denaturation (bubble breathing), deriving its dynamic response to external physical parameters and the DNA sequence in terms of the bubble relaxation time spectrum and the autocorrelation function of bubble breathing. The interaction with binding proteins that selectively bind to the DNA single strand exposed in a denaturation bubble are shown to involve an interesting competition of time scales, varying between kinetic blocking of protein binding up to full binding protein-induced denaturation of the DNA. We will also address the potential to use DNA physics for the design of nanosensors. Finally, we report recent findings on the search process of proteins for a specific target on the DNA. INTRODUCTION Biological macromolecules group into the rather unspecific molecules of the polysaccharide family (cellulose, chitin, starch) and the cytoskeletal polymers (actin, microtubules, intermediate filaments); and the highly specific biopolymers with their unique sequence of building blocks, namely, nucleic acids (DNA and RNA) and polypeptides (proteins). Nucleic acids and proteins are characterised by their specific biological function, and they are intimately connected through the central dogma of molecular biology according to which the information from the genome, given by the alphabet of bases along the DNA, is transferred to messenger RNA, and further converted to proteins [1, 2]. In turn, the proteins regulate the expression (reading out and conversion to protein) of a specific gene. Alternatively, a particular gene can be converted into transfer and ribosomal RNA that is not translated into proteins. Complementary to this picture, an RNA world is possible [2].
0899-N03-06.2
In this paper, we study some fundamental aspects of the physics of DNA and DNA-protein interactions. Specifically, we develop dynamical models for the local denaturation of DNA into transient, fluctuating bubbles as well as the interaction of specifically single stranded DNA-binding proteins with the single stranded DNA in these denaturation zones. DNA BREATHING Under physiological conditions the Watson-Crick double-helix is the thermodynamically stable configuration of a DNA molecule. This stability is effected by the specific Watson-Crick H-bonding, whose key-lock principle guarantees the high level of fidelity during replication and transcription; and by the stronger base-stacking between neighbouring base-pairs causing hydrophobic interactions between the planar aromatic bases [3, 4]. T
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