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Regensburg 2010 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 3: DNA, RNA and Associated Enzymes

BP 3.2: Vortrag

Montag, 22. März 2010, 14:30–14:45, H43

Effect of DNA sequence variation on the dynamics of backtracking during RNA transcription — •Abigail Klopper1,2, Justin Bois1,2, and Stephan Grill1,21Max Planck Institute for the Physics of Complex Systems — 2Max Planck Institute of Molecular Cell Biology and Genetics

The transcription of information encoded in the genome is facilitated by RNA polymerase, a macromolecular machine which steps along a DNA template, assembling and extruding a complementary RNA transcript. The process is typically marked by pausing events which have been linked to an inactive backtracked state, involving diffusive excursions of the polymerase along the template. In this state, the polymerase cannot elongate the RNA transcript, and productive synthesis only resumes once the polymerase has realigned with the RNA, effectively stepping out of the backtrack. Inability to recover can lead to cleavage of the transcript or termination of the process. We investigate the notion that sequence variation along the template influences the average time required for unassisted recovery. We perform simulations and numerical calculations using a hopping model with DNA sequence-specific transition rates. Motivated by results from single molecule experiments in which the polymerase is subject to mechanical force, we compute the sequence-averaged distribution of force-dependent pause recovery times. We show that DNA sequence variation rescales the distribution associated with a simple random walk and renders the polymerase less sensitive to the applied force.

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