Post-Translational Modifications by Lipid Metabolites during the DNA Damage Response and Their Role in Cancer

Guangrong Zhu; Xiangyang Zheng; Zhifeng Wang; Xingzhi Xu

doi:10.3390/biom12111655

Post-Translational Modifications by Lipid Metabolites during the DNA Damage Response and Their Role in Cancer

Biomolecules. 2022 Nov 8;12(11):1655. doi: 10.3390/biom12111655.

Authors

Guangrong Zhu^{1

2}, Xiangyang Zheng³, Zhifeng Wang¹, Xingzhi Xu¹

Affiliations

¹ Guangdong Key Laboratory for Genome Stability and Disease Prevention, Carson International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University School of Medicine, Shenzhen 518060, China.
² Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University School of Medicine, Shenzhen 518060, China.
³ Shenzhen University General Hospital-Dehua Hospital Joint Research Center on Precision Medicine, Dehua Hospital, Dehua, Quanzhou 362500, China.

Abstract

Genomic DNA damage occurs as an inevitable consequence of exposure to harmful exogenous and endogenous agents. Therefore, the effective sensing and repair of DNA damage are essential for maintaining genomic stability and cellular homeostasis. Inappropriate responses to DNA damage can lead to genomic instability and, ultimately, cancer. Protein post-translational modifications (PTMs) are a key regulator of the DNA damage response (DDR), and recent progress in mass spectrometry analysis methods has revealed that a wide range of metabolites can serve as donors for PTMs. In this review, we will summarize how the DDR is regulated by lipid metabolite-associated PTMs, including acetylation, S-succinylation, N-myristoylation, palmitoylation, and crotonylation, and the implications for tumorigenesis. We will also discuss potential novel targets for anti-cancer drug development.

Keywords: DNA damage response; N-myristoylation; S-succinylation; acetylation; cancer; crotonylation; lipid metabolites; palmitoylation; post-translational modification.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

DNA Damage
DNA Repair*
Genomic Instability
Humans
Lipids
Neoplasms* / genetics
Protein Processing, Post-Translational

Substances

Lipids

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant nos. 32090031, 31761133012, 31800683, and 31530016), the National Basic Research Program of China (grant no. 2017YFA0503900), and the Shenzhen Science and Technology Innovation Commission (grant nos. JCYJ20180507182213033 and JCYJ20170412113009742).