High nucleotide skew palindromic DNA sequences function as replication origins due to their unzipping propensity

TL;DR

This paper demonstrates that high nucleotide skew palindromic DNA sequences facilitate DNA unzipping, acting as replication origins due to their low melting barriers, supported by models and genomic evidence across various organisms.

Contribution

It introduces a Markov chain model to explain how sequence-dependent unzipping propensity of high-skew palindromic sequences enables their function as replication origins.

Findings

High-skew palindromic sequences have low kinetic barriers for melting.

Such sequences are enriched at replication origins in diverse organisms.

Model predictions align with genomic data from mitochondria, bacteria, archaea, and plasmids.

Abstract

Locations of DNA replication initiation in prokaryotes, called "origins of replication", are well-characterized. However, a mechanistic understanding of the sequence-dependence of the local unzipping of double-stranded DNA, the first step towards replication initiation, is lacking. Here, utilizing a Markov chain model that was created to address the directional nature of DNA unzipping and replication, we model the sequence dependence of local melting of double-stranded linear DNA segments. We show that generalized palindromic sequences with high nucleotide skews have a low kinetic barrier for local melting near melting temperatures. This allows for such sequences to function as replication origins. We support our claim with evidence for high-skew palindromic sequences within the replication origins of mitochondrial DNA, bacteria, archaea and plasmids.