The template-specific fidelity of DNA replication with high-order neighbor effects: a first-passage approach
arXiv:1901.01495 · doi:10.1103/PhysRevE.100.012131
Abstract
DNA replication fidelity is a critical issue in molecular biology. Biochemical experiments have provided key insights on the mechanism of fidelity control by DNAP in the past decades, whereas systematic theoretical studies on this issue began only recently. Because of the underlying difficulties of mathematical treatment, comprehensive surveys on the template-specific replication kinetics are still rare. Here we proposed a first-passage approach to address this problem, in particular the positional fidelity, for complicated processes with high-order neighbor effects. Under biologically-relevant conditions, we derived approximate analytical expressions of the positional fidelity which shows intuitively how some key kinetic pathways are coordinated to guarantee the high fidelity, as well as the high velocity, of the replication processes. It was also shown that the fidelity at any template position is dominantly determined by the nearest-neighbor template sequences, which is consistent with the idea that replication mutations are randomly distributed in the genome.
arXiv comment10 pages, 6 figures
References in corpus (7)
- Kinetics and thermodynamics of first-order Markov chain copolymerization
- Kinetics and thermodynamics of DNA polymerases with exonuclease proofreading
- Kinetics and thermodynamics of exonuclease-deficient DNA polymerases
- A general theory of kinetics and thermodynamics of steady-state copolymerization
- Growth and dissolution of macromolecular Markov chains
- Proofreading of DNA Polymerase: a new kinetic model with higher-order terminal effects
- First-passage problems in DNA replication: effects of template tension on stepping and exonuclease activities of a DNA polymerase motor