Scientists from the Institute of Molecular Genetics of the CAS in cooperation with collages from Caroline Institute in Stockholm have published a discovery, which looks again at what happens in our cells, when they lose their “guardian” – the essential protein p53. The results of their research, which was published by the prestigious EMBO Journal, could contribute to clarifying the causes of the accumulation of DNA failures and find application for instance in radiotherapy.

The human body has various mechanisms how to deal with disruptions, including genetic ones. It was assumed for a long time that if DNA damage occurs, the cells suspend their division until all malfunctions are repaired. However, the international team of researchers has now come to the conclusion that cell division can be restarted in some circumstances even earlier - before the necessary repairs are completed.

“Imagine it like an alarm clock: when the DNA damage is large, the alarm clock sets a long time for repair, and when it is lesser, it takes just a few minutes. But if the alarm rings, the cell division will start again, despite the fact that a few faults have not been corrected yet,” explains Libor Macůrek from the Laboratory of Cancer Cell Biology at the Institute of Molecular Genetics.

According to Macůrek, in this regard human cells resemble simple yeast cells, with which premature division is already known, it is labelled as adaptation. Unlike yeast, human cells luckily have much better protection: they contain the protein p53, a kind of “guardian of the genome”. In the case of a failure, it can “brake” the cell, and later then “release the brake” as soon as it is OK.

“The problem arises if the cell for some reasons loses the protein p53, which can happen for instance by accidental mutation. In that case, the risk of the transfer of undesirable changes and the emergence of tumours is much higher,” adds Macůrek, who conducted the research on healthy cells without p53. For the body, the absence of the protein p53 is a great threat: an example are patients with so-called Li-Fraumeni Syndrome, who fight with uncontrollable tumour growth in many parts of the body.

 A mathematical model that can predict the behaviour of cells exposed to ionizing radiation under laboratory conditions.

“I would not like to exaggerate our discovery in some way; I think it is another small fragment that helps clarify what is actually happening in our cells. It is then up to medicine to find a way how to treat these disorders,” Macůrek points out. With the help of newly created probes, scientists are more or less already able to measure very precisely the level of the signal caused by the damage of the DNA and record its spread by the cell nucleus in living cells. Based on this knowledge, even a mathematical model has been created that can predict the behaviour of cellsaccording to the level of DNA damage in a certain phase of the cell cycle.

Prepared by: Alice Horáčková in cooperation with the Institute of Molecular Genetics of the CAS
Photo: Institute of Molecular Genetics of the CAS and iStock