When big is bad: Excessive cell growth impairs genome homeostasis and induces cell senescence

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Several seminars are held weekly at the Instituto Gulbenkian de Ciência, an initiative that aims to bring together all researchers around the topics under discussion.

The sessions, with internal researchers or guests, contribute to stimulate the open and extremely collaborative culture of the IGC.

You can read the abstract of this seminar to learn more about it.


Cell size is tightly controlled in all cells, suggesting that having a specific size is critical for cell function. Interestingly, there is a strong correlation between cell size and DNA content between different species, but also between cells of the same species. These observations suggest that maintaining a constant DNA:cytoplasm ratio is critical for cell function. How this relationship is established and why it is important is poorly understood. Using reversible cell cycle blocks in yeast and human cells, we were able to show that a large increase in cell size in the absence of DNA synthesis leads to an impaired DNA damage response that severely impairs genome repliation and drives cells into senescence. In addition, we find that the DNA of enlarged cells becomes more prone to breaking, suggesting that chromatin organization is fundamentally altered in enlarged cells. Together our data indicate that a low DNA:cytoplasm ratio is detrimental for genome maintenance and cell fitness.


Gabriel Neurohr
Institute of Biochemistry, ETH Zurich


Marco Fumasoni

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