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2006

Time: Wednesday, Oct. 4, 2006 at 2:30 PM in MC 204

DNA conformations and function

Prof. Ralf Metzler, Canada Research Chair in Biological Physics
Dept. of Physics, University of Ottawa, Ottawa, Canada

Abstract:
Thermal motion within the double helix plays a critical role in DNA structure and function. On a small scale, base-pair openings represent the most dramatic deviations from the double helix ground state. Although rare, the events of single stranded bubble formation make the active groups of DNA bases accessible for interaction with proteins or chemicals. The opening and closing dynamics of these bubbles can be monitored both by NMR techniques, and fluorescence measurements on a single DNA level. A dynamical model will be presented, relating the sequence of base-pairs to the opening probabilities and the bubble dynamics. It will be shown how the bubble dynamics competes with the binding of proteins to DNA single-strand, and the connection between bubble dynamics and transcription initiation will be discussed. Fluctuating bubbles may be used as molecular beacons in nanosensing applications, or, interacting with stabilising chemicals or proteins, to store information.

The majority of biological functions of DNA, and potential technological applications, rely on site-specific DNA-binding proteins finding their targets, and therefore searching efficiently through megabases of non-target DNA. A particular case is gene expression. I will introduce some recent advances in the understanding of the target search, and how it relates to the local and global conformations of the DNA molecule.

References:

  1. R Metzler, T Ambjoernsson, A Hanke, Y Zhang, and S Levene, E-print physics/0609139
  2. T Ambjoernsson, SK Banik, O Krichevsky, and R Metzler, Phys Rev Lett, at press (2006); E-print q-bio.BM/0608036.
  3. A Bakk and R Metzler, FEBS Lett 563, 66 (2004).
  4. MA Lomholt, T Ambjoernsson, and R Metzler, Phys Rev Lett 95, 260603 (2005); E-print cond-mat/0510072.
  5. HC Fogedby and R Metzler, E-print cond-mat/0608458.
  6. E Ercolini et al, E-print cond-mat/0609084.
  7. E Ercolini et al, E-print cond-mat/0609084.
  8. R Metzler and J Klafter, Phys Rep 339, 1 (2000); J Phys A 37 R161 (2004).