A temperature-driven DNA discrimination strategy to distinguish E. coli DNA and phage 5hmC-modified DNA
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The arms race between phages and bacteria is dynamic and ongoing, with both continuously acquiring new strategies to outcompete each other during co-evolution. Here, we report bacteriophage T4 exonuclease DexA and an uncharacterized Escherichia coli exonuclease as a rare pair of attack and defense duo arising from the same mechanism. DexA, highly conserved among phages, has two well-characterized biological roles: host DNA scavenging and intron homing. Unmodified DNA is the substrate during host DNA scavenging, whereas cleavage of 5hmC (5-hydroxymethylcytosine)-modified phage DNA is required for intron homing. We reveal a temperature-driven quaternary fold switch between DexA dimer and tetramer that facilitates cleavage of distinct DNA forms, namely 5hmC-modified phage DNA and unmodified host DNA. As a countermeasure, bacteria produce DexA variants for defense against phage that only targets 5hmC-modified DNA. Thus, both phages and bacteria compete using HmC-Recognizing EXonuclease strategies (designated as HREX).
Date Issued
2025-06-24
Date Acceptance
2025-05-28
Citation
Nucleic Acids Research, 2025, 53 (11)
ISSN
0305-1048
Publisher
Oxford University Press
Journal / Book Title
Nucleic Acids Research
Volume
53
Issue
11
Copyright Statement
© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
10.1093/nar/gkaf501
Publication Status
Published
Article Number
gkaf501
Date Publish Online
2025-06-11