Modeling translocation dynamics of strand displacement DNA synthesis by DNA polymerase I

J Mol Model. 2012 May;18(5):1951-60. doi: 10.1007/s00894-011-1222-1. Epub 2011 Aug 26.

Abstract

A model is presented for the translocation dynamics of the strand displacement DNA synthesis by DNA polymerases such as polymerase I family. (i) The model gives an explanation to the experimental results which showed that the rate of strand displacement DNA synthesis is nearly consistent with that of single stranded primer extension synthesis, although the two are expected to have substantial differences in their energetics. (ii) During strand displacement DNA synthesis, the pausing at the specific sequence is considered to be due to an affinity of the fingers subdomain for the specific sequence of dsDNA downstream of the single strand. The theoretical results on the sequence-dependent pausing dynamics such as the mean pausing lifetimes and the distribution of the pausing lifetime are consistent with the experimental data. Moreover, predicted results are presented for the binding affinity of the fingers subdomain for the specific sequence of dsDNA and the dependence of the mean sequence-dependent pausing lifetime on the external force acting on the polymerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Binding Sites
  • DNA / biosynthesis
  • DNA / chemistry*
  • DNA Polymerase I / chemistry*
  • DNA Polymerase I / genetics
  • DNA Replication / genetics
  • DNA, Single-Stranded / chemistry*
  • Kinetics
  • Molecular Dynamics Simulation*
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation

Substances

  • Bacterial Proteins
  • DNA, Single-Stranded
  • DNA
  • DNA Polymerase I