The template-specific fidelity of DNA replication with high-order neighbor effects: a first-passage approach

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...

Full description

Saved in:
Bibliographic Details
Published in:arXiv.org 2019-04
Main Authors: Qiu-Shi, Li, Pei-Dong, Zheng, Yao-Gen, Shu, Ou-Yang, Zhong-Can, Li, Ming
Format: Article
Language:English
Subjects:
Deoxyribonucleic acid
DNA
Iterative algorithms
Iterative methods
Molecular biology
Mutation
Replication
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2331-8422
DOI:10.48550/arxiv.1901.01495