A study has shed new light on the hidden mechanisms that govern when cells divide – mechanisms that underpin the propagation of life, and that go awry in cancer.
Ground-breaking new research, from scientists at The Institute of Cancer Research, London, and the University of Oxford, gives several new insights into the processes controlling cell division.
In particular, it clarifies the role of a phase of the cell life cycle called the ‘restriction point’ in cell division.
It also implicates a protein called p21 in the stop/go ‘decision’ made by cells to divide or not, depending on growth signals and damage to their DNA.
Mathematical predictions were confirmed with experiments
In the study, the researchers created a detailed mathematical model that accurately predicts when human cells will divide.
The model used large sets of data to predict whether normal human cells would divide, depending on the effect of changing the levels of different proteins.
Once the model had suggested roles for different proteins at different points in the cell lifecycle, the scientists confirmed the predictions in painstaking experiments on single cells.
The research was published in the Proceedings of the National Academy of Sciences (PNAS), one of the world’s top scientific journals, and was funded by a Strategic LoLa grant from the Biotechnology and Biological Sciences Research Council.
The process of cell division is strictly controlled to ensure cells divide correctly and at the right time. Competing mechanisms tell it to go, or stop, depending on circumstances in the cells.
The decision not to grow is essential to prevent new cells accumulating DNA damage that can lead to cancer.
Many cancers can have faults that help them survive DNA damage and to keep growing even with harmful mutations.
Window of opportunity in cell division
The study confirmed two points in the cell cycle where the decision for cell growth is taken: the restriction point and the G/1S transition.
It also showed that a boost in the amount of p21 protein at the right time provides cells with a window of opportunity, where the decision for cell growth can still be reversed if a cell is exposed to further DNA damage.
The researchers saw p21 can reverse the decision to divide in response to DNA damage in healthy cells – but when p21 was removed cells continued to divide, even if collecting potentially harmful mistakes in their DNA.
The most accurate prediction yet
Study co-leader Dr Chris Bakal, Team Leader in Dynamical Cell Systems at the ICR, said:
“Our model provides us with robust predictions about how cells respond to growth signals and DNA damage, giving us the most accurate picture yet of how a complex system of competing signalling proteins lead cells to ‘decide’ whether or not to divide.
“This research could help to identify ways to stop cancer cells from dividing, or get rid of checks cancer cells use on their own DNA damage to survive, pushing them into cell death.”
This article has been republished from materials provided by ICR. Note: material may have been edited for length and content. For further information, please contact the cited source.
Heldt, F. S., Barr, A. R., Cooper, S., Bakal, C., & Novák, B. (2018). A comprehensive model for the proliferation–quiescence decision in response to endogenous DNA damage in human cells. Proceedings of the National Academy of Sciences, 115(10), 2532-2537. doi:10.1073/pnas.1715345115