ELECTROSTATIC FORCES IN DNA BENDING BY PROTEINS

Project: Research project

Project Details

Description

DNA is often bent when complexed with proteins. Understanding the forces responsible for DNA bending in such complexes is of fundamental value in exploring and predicting the interplay of these macromolecules. An experimental approach has been devised to test the hypothesis that proteins with cationic surfaces can induce substantial DNA bending simply by neutralizing phosphates on one DNA face. Repulsions between phosphates in the remaining anionic helix are predicted to result in an unbalanced compression force acting to deform the DNA toward the protein. This hypothesis is supported by the results of electrophoretic experiments in which DNA spontaneously bends when one helical face is partially modified by incorporation of neutral phosphate analogs. Phasing with respect to a site of intrinsic DNA curvature (A6 tract) permits estimation of the electrostatic bend angle, and demonstrates that such modified DNAs are deformed toward the neutralized surface, as predicted& It is proposed to extend these studies to (i) more fully characterize how various arrangements of neutralized phosphates cause DNA bending, and (ii) apply this model to real examples of DNA bending by proteins. Four specific aims are described in this proposal: l. Determine how the distribution and sequence of phosphate neutralizations affect DNA bending; 2. Apply the bending model to specific DNA sequences known to be bent by proteins; 3. Analyze zwitterionic nucleotides as an alternative to neutral phosphate analogs, 4. Design and test two sequence-specific DNA bending proteins. These studies seek to explore one of the general principles that may explain DNA bending in nucleoprotein complexes.
StatusFinished
Effective start/end date9/1/9512/31/04

Funding

  • National Institutes of Health: $202,375.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $214,530.00
  • National Institutes of Health
  • National Institutes of Health: $220,884.00
  • National Institutes of Health: $208,364.00

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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