Protein Lysine Lactylation in DNA Damage Response: Regulatory Mechanisms and Emerging Functions
- 1State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China
- 2Department of Otorhinolaryngology Head and Neck Surgery, Molecular and Cellular Oncology, University Medical Center Mainz, 55131 Mainz, Germany
Abstract
Genomic DNA is constantly exposed to endogenous and exogenous stresses that can cause different types of DNA damage. DNA double-strand breaks (DSBs) are among the most damaging forms of DNA lesions, as persistent breaks can compromise genome stability. In response to such damage, cells activate DNA damage response (DDR) pathways that detect lesions and promote their repair. Lysine lactylation (Kla), a recently identified lysine acylation modification, links cellular metabolism and DNA repair. Recent evidence suggests that Kla may influence DDR by modulating the stability, interactions, and activity of DNA repair proteins. This review discusses recent advances in our understanding of lactylation in homologous recombination (HDR) and non-homologous end joining (NHEJ). We focus on MRE11, NBS1, BLM, and XLF lactylation and their roles in DNA repair and tumor chemoresistance. These findings suggest that lactylation can affect genome stability, tumor progression, and responses to cancer therapy by regulating key DDR factors. However, how lactylation is regulated during DDR and how it affects DNA repair remain largely unclear. Further studies are needed to elucidate how DNA damage-induced lactylation can be regulated, the functions of lactylation writers and erasers, and the significance of lactylation in various disease contexts.
Related
- Super-enhancers: regulatory mechanisms, biological functions, diseases, and therapeutic targets.
- Lactate dynamics at the Pseudomonas aeruginosa–host interface: bacterial metabolism, host defense, and emerging links to histone lactylation
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications
- Emerging regulatory role of lncRNA MALAT1 in bone homeostasis: from the β–catenin–OPG/Jagged1 signalling axis to a broader regulatory network
- Preface to the special issue “Cytoplasmic Genome Regulation: Genomes and Regulatory Mechanisms of Chloroplasts and Mitochondria”
BibTeX
@article{pei2026protein,
title = {{Protein Lysine Lactylation in DNA Damage Response: Regulatory Mechanisms and Emerging Functions}},
author = {Xinke Pei and Jinhui Zhang and Yue Gao and Zuo Pan and Yue Wang and Luyu Wang and Zhenguo Wang and Guo-Bin Ding and Roland H. Stauber and Ting Ni and Shuailin Hao},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101528},
url = {https://www.mdpi.com/2218-273X/16/10/1528},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Protein Lysine Lactylation in DNA Damage Response: Regulatory Mechanisms and Emerging Functions
AU - Xinke Pei
AU - Jinhui Zhang
AU - Yue Gao
AU - Zuo Pan
AU - Yue Wang
AU - Luyu Wang
AU - Zhenguo Wang
AU - Guo-Bin Ding
AU - Roland H. Stauber
AU - Ting Ni
AU - Shuailin Hao
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101528
UR - https://www.mdpi.com/2218-273X/16/10/1528
AB - Genomic DNA is constantly exposed to endogenous and exogenous stresses that can cause different types of DNA damage. DNA double-strand breaks (DSBs) are among the most damaging forms of DNA lesions, as persistent breaks can compromise genome stability. In response to such damage, cells activate DNA damage response (DDR) pathways that detect lesions and promote their repair. Lysine lactylation (Kla), a recently identified lysine acylation modification, links cellular metabolism and DNA repair. Recent evidence suggests that Kla may influence DDR by modulating the stability, interactions, and activity of DNA repair proteins. This review discusses recent advances in our understanding of lactylation in homologous recombination (HDR) and non-homologous end joining (NHEJ). We focus on MRE11, NBS1, BLM, and XLF lactylation and their roles in DNA repair and tumor chemoresistance. These findings suggest that lactylation can affect genome stability, tumor progression, and responses to cancer therapy by regulating key DDR factors. However, how lactylation is regulated during DDR and how it affects DNA repair remain largely unclear. Further studies are needed to elucidate how DNA damage-induced lactylation can be regulated, the functions of lactylation writers and erasers, and the significance of lactylation in various disease contexts.
SN - 2218-273X
ER -