Tuning and switching a DNA polymerase motor with mechanical tension
AUTOR(ES)
Goel, Anita
FONTE
National Academy of Sciences
RESUMO
Recent single-molecule experiments reveal that mechanical tension on DNA can control both the speed and direction of the DNA polymerase motor. We present a theoretical description of this tension-induced “tuning” and “switching.” The internal conformational states of the enzyme motor are represented as nodes, and the allowed transitions between states as links, of a biochemical network. The motor moves along the DNA by cycling through a given sequence of internal states. Tension and other external control parameters, particularly the ambient concentrations of enzyme, nucleotides, and pyrophosphates, couple into the internal conformational dynamics of the motor, thereby regulating the steady-state flux through the network. The network links are specified by bulk-phase kinetic data (in the absence of tension), and rudimentary models are used to describe the dependence on tension of key links. We find that this network analysis simulates well the chief results from single-molecule experiments including the tension-induced attenuation of polymerase activity, the onset of exonucleolysis at high tension, and insensitivity to large changes in concentration of the enzyme. A major dependence of the switching tension on the nucleotide concentration is also predicted.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=187828Documentos Relacionados
- Tuning DNA “strings”: Modulating the rate of DNA replication with mechanical tension
- Template-switching during DNA synthesis by Thermus aquaticus DNA polymerase I.
- Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions
- In vivo RNA-directed transcription, with template switching, by a mammalian RNA polymerase
- Effect of Mechanical Cycling on Screw Torque in External Hexagon Implants with and without Platform Switching