1301.1876 (Ajeet K. Sharma et al.)

First-passage problems in DNA replication: effects of template tension
on stepping and exonuclease activities of a DNA polymerase motor    [PDF]

Ajeet K. Sharma, Debashish Chowdhury

A DNA polymerase (DNAP) replicates a template DNA strand. It also exploits the template as the track for its own motor-like mechanical movement. In the polymerase mode it elongates the nascent DNA by one nucleotide in each step. But, whenever it commits an error by misincorporting an incorrect nucleotide, it can switch to an exonuclease mode. In the latter mode it excises the wrong nucleotide before switching back to its polymerase mode. We capture the effects of mechanical tension $F$ applied on the template DNA within the framework of a stochastic kinetic model of DNA replication. The model mimics an {\it in-vitro} experiment where a single DNAP converts a ssDNA template into a dsDNA by its action. The $F$-dependence of the average rate of replication, which includes also the effects of correction of misincorporations, is in good qualitative agreement with the corresponding experimental results. Using the methods of first-passage times for same model, we also derive the exact analytical expressions for the probability distributions of nine distinct conditional dwell times of a DNAP. The predicted tension-dependence of these distributions are, in principle, accessible to single-molecule experiments.

View original: http://arxiv.org/abs/1301.1876