# The role of histone modifications in transcription regulation upon DNA damage

## TL;DR

This review explains how changes to histone proteins help control gene activity during DNA damage, which is important for preventing diseases like cancer.

## Contribution

The paper provides a comprehensive overview of how specific histone modifications regulate transcription during DNA damage response.

## Key findings

- Histone modifications like phosphorylation and acetylation control DNA accessibility for repair.
- Dysregulation of these modifications is linked to cancer and neurodegenerative diseases.
- Understanding these mechanisms can guide the development of new therapeutic strategies.

## Abstract

Cells are constantly exposed to various sources of DNA damage, including radiation, chemicals, replicative stress and oxidative stress, that threaten genome stability. To ensure faithful DNA repair, transcription regulation needs to be tightly controlled. This regulation involves transcriptional suppression, selective activation of DNA repair‐related genes and transcriptional recovery post‐repair. Failure to properly modulate transcription during DNA damage can result in collisions between transcriptional and repair machineries, misregulation of repair genes and delayed recovery, ultimately compromising genomic integrity. Chromatin modifications play a central role in this process. These modifications include phosphorylation, methylation, acetylation and ubiquitination, which orchestrate DNA accessibility for repair machinery and fine‐tune transcriptional responses. Absence of these modifications leads to inefficient DNA repair and transcriptional errors that are implicated in diseases such as cancer, premature ageing and neurodegenerative disorders. In this review, we delve into the role of various types of histone modifications, such as phosphorylation, methylation, acetylation and ubiquitination and how they regulate transcription in response to DNA damage.

Impact StatementThis review elucidates how histone modifications orchestrate transcription regulation during DNA damage response, safeguarding genome stability. We also discuss transcription dysregulation in diseases such as cancer and premature aging. Our review provide insights on chromatin‐based repair pathways and guide researchers in developing therapeutic targets.

This review elucidates how histone modifications orchestrate transcription regulation during DNA damage response, safeguarding genome stability. We also discuss transcription dysregulation in diseases such as cancer and premature aging. Our review provide insights on chromatin‐based repair pathways and guide researchers in developing therapeutic targets.

This review discusses the critical role of histone modifications in regulating gene expression during the DNA damage response (DDR). By modulating chromatin structure and recruiting repair factors, these post‐translational modifications fine‐tune transcriptional programmes to maintain genomic stability. Understanding these mechanisms provides insights into diseases like cancer and highlights potential therapeutic targets. Created in biorender. Wang, S. (2026) https://BioRender.com/hddjovi