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TPI and GAPDH Interact with Rad9, Linking Glycolytic Enzymes to Cancer
Vivienne X Y Chua1, Joyce M X Yip1, Melody T K Cho1
1Norbert Lehming, Department of Microbiology & Immunology and Cancer Programme at NUSMED, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Block MD4, Level 5, Singapore 117545, Singapore.
International Journal of Molecular Sciences
|June 26, 2026
Summary
Cancer cells utilize aerobic glycolysis, producing lactate that aids DNA repair and promotes resistance to radiotherapy. Yeast studies reveal glycolytic enzymes TPI and GAPDH interact with DNA repair proteins, enabling cancer cell proliferation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Cancer cells exhibit aerobic glycolysis, a less efficient process than respiration, to produce biomolecules for proliferation.
- Aerobic glycolysis generates lactate, which modifies DNA repair enzymes via lysine lactylation, conferring radioresistance to cancer cells.
- Current therapies combining radiotherapy and chemotherapy face challenges due to lactate's effects on DNA repair.
Purpose of the Study:
- To investigate the role of glycolytic enzymes in DNA damage response and cancer proliferation using yeast as a model.
- To explore the interaction between glycolysis and DNA repair mechanisms in the context of cancer.
Main Methods:
- Utilized yeast as a model organism to study glycolysis and DNA repair.
- Investigated interactions between glycolytic enzymes (TPI, GAPDH) and DNA damage-dependent checkpoint proteins (Rad9p).
- Generated and analyzed tpi and gapdh mutant yeast strains deficient in DNA repair.
Main Results:
- Discovered interactions between yeast glycolytic enzymes Tpi1p/Tdh1-3p and the DNA damage checkpoint protein Rad9p.
- Proposed that Tpi1p and Tdh1-3p can override Rad9p, allowing proliferation of cells with damaged DNA.
- Identified tpi and gapdh mutant strains with impaired DNA repair, with gapdh mutants showing normal enzymatic activity.
Conclusions:
- Glycolytic enzymes TPI and GAPDH play a role in overriding DNA damage checkpoints, potentially contributing to cancer cell proliferation.
- GAPDH exhibits moonlighting functions in DNA damage response, independent of its glycolytic activity.
- Further research is needed to understand the complex relationship between glycolysis, DNA repair, and cancer.
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