# Molecular Mechanisms of DNA Damage Response and Epigenetic Regulation in Cold-Adapted Species: Implications for Genome Stability and Molecular Network Perspective

## TL;DR

This review explores how cold-adapted species protect their DNA during freezing and thawing, using repair and epigenetic mechanisms to maintain genome stability.

## Contribution

The paper integrates DDR and epigenetic mechanisms into a molecular network perspective for environmental resilience in cold-adapted species.

## Key findings

- Cold-adapted species activate BER, NER, HR, and NHEJ pathways to repair DNA damage during freeze–thaw cycles.
- Epigenetic regulators like DNMTs and HDACs modulate chromatin and DDR signaling during recovery.
- Conservation of these adaptive pathways is observed across freeze-tolerant vertebrates, hibernating mammals, and polar fish.

## Abstract

Cold-adapted species display remarkable genomic resilience under prolonged freezing and thawing cycles that would be lethal to most organisms. This review synthesizes current knowledge on the molecular mechanisms of DNA damage response (DDR) and epigenetic regulation that collectively safeguard genome integrity in these organisms. We highlight key DNA repair pathways, including base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR), and non-homologous end joining (NHEJ), that are activated during freeze–thaw stress to repair oxidative and strand break damage. Epigenetic regulators such as DNA methyltransferases (DNMTs), histone methyltransferases, and histone deacetylases (HDACs) dynamically remodel chromatin and modulate DDR signaling, facilitating efficient repair and transcriptional reprogramming during recovery. Comparative evidence from freeze-tolerant vertebrates, hibernating mammals, and polar fish underscores the conservation of these adaptive pathways across taxa. Integrating these insights provides a molecular network perspective (MNP) linking DDR and epigenetic mechanisms to environmental resilience, with potential applications in crop improvement and biotechnological adaptation strategies for extreme environments.