Kinetics and thermodynamics of exonuclease-deficient DNA polymerases

Abstract

A kinetic theory is developed for exonuclease-deficient DNA polymerases, based on the experimental observation that the rates depend not only on the newly incorporated nucleotide, but also on the previous one, leading to the growth of Markovian DNA sequences from a Bernoullian template. The dependences on nucleotide concentrations and template sequence are explicitly taken into account. In this framework, the kinetic and thermodynamic properties of DNA replication, in particular, the mean growth velocity, the error probability, and the entropy production in terms of the rate constants and the concentrations are calculated analytically. Theory is compared with numerical simulations for the DNA polymerases of T7 viruses and human mitochondria.

Kinetics and thermodynamics of living copolymerization processes

“…This allows us to set up kinetic models, which can be solved with the aforementioned methods [29,30]. Typically, exonuclease-deficient polymerases have an error probability in the range 10 −6 -10 −5 η 10 −2 [29]. With exonuclease, DNA polymerases have a proofreading activity, reducing the error probability to the range 10 −8 η 10 −6 -10 −5 [30].…”

“…The kinetic parameters of the 16 possible pairings have been experimentally measured for several DNA polymerases, including the human mitochondrial one [28]. This allows us to set up kinetic models, which can be solved with the aforementioned methods [29,30]. Typically, exonuclease-deficient polymerases have an error probability in the range 10 −6 -10 −5 η 10 −2 [29].…”

Template-specific fidelity of DNA replication with high-order neighbor effects: A first-passage approach

“…The basic theory in Sec.II can be slightly modified to handle these problems without appealing for additional steadystate assumptions which are usually adopted to model multi-step processes in biochemistry (e.g, the well known Michaelis-Menten kinetics which is also used to study the DNA replication in Ref. [14]). Comprehensive discussions on this issue, as well as applications to real DNA replication systems, will be presented elsewhere.…”

Kinetic discrimination of a polymerase in the presence of obstacles

“…When a system is driven away from equilibrium, copying fidelity can be enhanced at the cost of additional dissipation. A theory of the fidelity of transcription will inevitably investigate such processes from a thermodynamical perspective.Several recent papers were devoted to this question [4][5][6][7][8][9]. Sartori and Pigolotti [4] discussed the difference between the energetic discrimination scheme that was mentioned above and kinetic discrimination.…”

“…The thermodynamics of polymerization processes were studied meticulously by Andrieux and Gaspard in a series of papers [5][6][7][8][9]. For copolymerization on a template with kinetic discrimination, their model showed trade-off between accuracy and dissipation.…”