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

The 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...

Full description

Saved in:
Bibliographic Details
Published in:International journal of biological macromolecules 2024-04, Vol.264 (Pt 1), p.130351-130351, Article 130351
Main Authors: Zhu, Zhuang, Li, Shaoming, Yin, Xiaopeng, Sun, Kai, Song, Jianzhong, Ren, Wenhao, Gao, Ling, Zhi, Keqian
Format: Article
Language:English
Subjects:
Acetylglucosamine - metabolism
Cancer
DNA - metabolism
DNA Damage
DNA damage response
DNA Repair
Neoplasms - drug therapy
Neoplasms - genetics
O-GlcNAcylation
Protein Processing, Post-Translational
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The 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. [Display omitted]
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2024.130351