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Updated: Jun 26, 2026

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells
Published on: June 9, 2020
The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways
L Mattera1, F Escaffit, M-J Pillaire
1LBCMCP, CNRS, Toulouse, Franc.
Abstract:
The Tip60 histone acetyltransferase belongs to a multimolecular complex that contains many chromatin remodeling enzymes including the ATPase p400, a protein involved in nucleosomal incorporation of specific histone variants and that can directly or indirectly repress some Tip60-dependent pathways. Tip60 activity is critical for the cellular response to DNA damage and is affected during cancer progression. Here, we found that the ratio between Tip60 and p400 mRNAs is affected in most colorectal carcinoma. Strikingly, reversing the p400/Tip60 imbalance by Tip60 overexpression or the use of siRNAs resulted in increased apoptosis and decreased proliferation of colon-cancer-derived cells, suggesting that this ratio defect is important for cancer progression. Furthermore, we demonstrate that the p400/Tip60 ratio controls the oncogene-induced DNA damage response, a known anticancer barrier. Finally, we found that it is also critical for the response to 5-fluorouracil, a first-line treatment against colon cancer. Together, our data indicate that the p400/Tip60 ratio is critical for colon cancer cells proliferation and response to therapeutic drugs through the control of stress-response pathways.
Insights
The ratio of Tip60 and p400 proteins is altered in colorectal cancer, impacting cell growth and DNA damage response. Restoring this balance inhibits cancer progression and improves drug response.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Tip60 histone acetyltransferase is crucial for DNA damage response and is implicated in cancer.
- The ATPase p400 is part of the Tip60 complex and can modulate its activity.
- Tip60 and p400 interactions are vital for cellular pathways affected in cancer progression.
Purpose of the Study:
- To investigate the role of the Tip60/p400 mRNA ratio in colorectal carcinoma.
- To determine if modulating this ratio impacts colon cancer cell behavior and therapeutic response.
Main Methods:
- Analysis of Tip60 and p400 mRNA levels in colorectal cancer samples.
- Experimental manipulation of Tip60/p400 ratio using overexpression and siRNA.
- Assessment of apoptosis, proliferation, and DNA damage response in colon cancer cells.
Main Results:
- The Tip60/p400 mRNA ratio is dysregulated in most colorectal carcinomas.
- Correcting the Tip60/p400 imbalance increases apoptosis and reduces proliferation in colon cancer cells.
- The Tip60/p400 ratio influences the oncogene-induced DNA damage response and sensitivity to 5-fluorouracil.
Conclusions:
- The Tip60/p400 ratio is a critical factor in colon cancer cell proliferation and response to therapy.
- This ratio's control over stress-response pathways is key to its role in cancer progression and drug sensitivity.
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