Zhuang Zhu, Shaoming Li, Xiaopeng Yin, Kai Sun, Jianzhong Song, Wenhao Ren, Ling Gao, Keqian Zhi
International journal of biological macromolecules 2024 AprThe DNA damage response (DDR) safeguards the stable genetic information inheritance by orchestrating a complex protein network in response to DNA damage. However, this mechanism can often hamper the effectiveness of radiotherapy and DNA-damaging chemotherapy in destroying tumor cells, causing cancer resistance. Inhibiting DDR can significantly improve tumor cell sensitivity to radiotherapy and DNA-damaging chemotherapy. Thus, DDR can be a potential target for cancer treatment. Post-translational modifications (PTMs) of DDR-associated proteins profoundly affect their activity and function by covalently attaching new functional groups. O-GlcNAcylation (O-linked-N-acetylglucosaminylation) is an emerging PTM associated with adding and removing O-linked N-acetylglucosamine to serine and threonine residues of proteins. It acts as a dual sensor for nutrients and stress in the cell and is sensitive to DNA damage. However, the explanation behind the specific role of O-GlcNAcylation in the DDR remains remains to be elucidated. To illustrate the complex relationship between O-GlcNAcylation and DDR, this review systematically describes the role of O-GlcNAcylation in DNA repair, cell cycle, and chromatin. We also discuss the defects of current strategies for targeting O-GlcNAcylation-regulated DDR in cancer therapy and suggest potential directions to address them. Copyright © 2024. Published by Elsevier B.V.
Zhuang Zhu, Shaoming Li, Xiaopeng Yin, Kai Sun, Jianzhong Song, Wenhao Ren, Ling Gao, Keqian Zhi. Review: Protein O-GlcNAcylation regulates DNA damage response: A novel target for cancer therapy. International journal of biological macromolecules. 2024 Apr;264(Pt 1):130351
PMID: 38403231
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