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Review: Protein O-GlcNAcylation regulates DNA damage response: A novel target for cancer therapy

Zhuang Zhu1, Shaoming Li1, Xiaopeng Yin2

  • 1Department of Oral and Maxillofacial Reconstruction, the Affiliated Hospital of Qingdao University, Qingdao 266555, China; School of Stomatology, Qingdao University, Qingdao 266003, China; Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Qingdao 266555, China.

International Journal of Biological Macromolecules
|February 25, 2024
PubMed

Insights

Targeting the DNA damage response (DDR) pathway is crucial for cancer therapy. This review explores how O-GlcNAcylation, a key post-translational modification, influences DDR and impacts cancer treatment effectiveness.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cancer Research

Background:

  • The DNA damage response (DDR) is vital for maintaining genomic stability but can lead to cancer treatment resistance.
  • Post-translational modifications (PTMs), including O-GlcNAcylation, regulate DDR protein activity.
  • O-GlcNAcylation is sensitive to cellular stress and nutrient status, suggesting a role in DDR.

Purpose of the Study:

  • To elucidate the intricate role of O-GlcNAcylation in the DNA damage response (DDR).
  • To review the impact of O-GlcNAcylation on DNA repair, cell cycle progression, and chromatin regulation.
  • To discuss current therapeutic strategies targeting O-GlcNAcylation in cancer and propose future directions.

Main Methods:

  • Systematic review of existing literature on O-GlcNAcylation and DDR.
  • Analysis of the interplay between O-GlcNAcylation and key DDR pathways.
  • Discussion of therapeutic implications and challenges.

Main Results:

  • O-GlcNAcylation significantly modulates the function of DDR proteins.
  • This modification influences DNA repair efficiency, cell cycle checkpoints, and chromatin accessibility.
  • Dysregulation of O-GlcNAcylation can impact cancer cell sensitivity to genotoxic therapies.

Conclusions:

  • O-GlcNAcylation is a critical regulator of the DNA damage response.
  • Targeting O-GlcNAcylation presents a promising, yet complex, strategy for enhancing cancer therapy.
  • Further research is needed to fully understand and exploit O-GlcNAcylation-mediated DDR modulation for clinical benefit.
Keywords:
CancerDNA damage responseO-GlcNAcylation

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