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An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
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Epigenetic Dysregulation in Cancer: Implications for Gene Expression and DNA Repair-Associated Pathways

Nina Rembiałkowska1, Katarzyna Rekiel2, Piotr Urbanowicz2

  • 1Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.

International Journal of Molecular Sciences
|July 12, 2025
PubMed

Insights

Epigenetic modifications impact DNA repair and genomic stability. Aberrant epigenetic patterns in cancer impair DNA repair pathways, offering new therapeutic targets for drug-resistant cancers.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Biology

Background:

  • Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, are crucial regulators of chromatin architecture and gene expression.
  • These modifications influence DNA repair mechanisms, maintaining genomic stability.
  • Aberrant epigenetic patterns are increasingly recognized in cancer development and progression.

Purpose of the Study:

  • To review recent advances in understanding epigenetic dysfunction and its impact on DNA repair.
  • To explore how epigenetic alterations impair key DNA repair pathways in cancer.
  • To highlight the therapeutic potential of targeting epigenetic dysregulation for cancer treatment.

Main Methods:

  • Literature review of recent studies on epigenetics and DNA repair.
  • Analysis of the roles of DNA methylation, histone modifications, and non-coding RNAs in DNA repair.
  • Examination of chromatin-remodeling complexes and their function in DNA damage response.
  • Discussion of nanoparticle-mediated delivery strategies for epigenetic therapies.

Main Results:

  • Epigenetic modifications profoundly influence DNA repair, affecting homologous recombination (HR), non-homologous end joining (NHEJ), and base excision repair (BER).
  • Cancer-associated epigenetic changes suppress key repair genes and hinder access to DNA break sites, compromising repair efficiency.
  • Mutations in chromatin-remodeling complexes disrupt nucleosome repositioning, impairing damage sensing and repair machinery assembly.
  • Non-coding RNAs contribute to epigenetic silencing at DNA break sites, exacerbating repair deficiencies.

Conclusions:

  • Epigenetic dysregulation significantly impairs DNA repair mechanisms in cancer.
  • Targeting epigenetic alterations in DNA repair pathways presents a promising strategy for developing more effective and drug-resistant cancer therapies.
  • Nanoparticle delivery systems offer potential to overcome pharmacologic resistance in epigenetic cancer treatments.
Keywords:
DNA repair mechanismschromatin remodelingdrug resistance in cancerepigenetic therapynon-coding RNA

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