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Biologists discover part of mechanism behind cell ageing

A study by scientists from the MU Faculty of Medicine and FNUSA-ICRC has been published in the journal Nature.

Lumír Krejčí

The human body is made up of cells, which are far more complicated than most people might remember from high school biology classes. The mechanisms that enable the functioning and creation of new cells through division are so complicated that they have yet to be fully described.

Biologists from the Faculty of Medicine of Masaryk University and the International Clinical Research Center of St. Anne's University Hospital Brno (FNUSA-ICRC) together with colleagues from Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL) have discovered an important part of the cell division process, which might help understand the creation of cancer cells and cell ageing. In a paper published in the prestigious scientific journal Nature, these researchers describe a mechanism that facilitates the stability or the extension of chromosome ends, which are known as telomeres.

An organism’s DNA holds all the information necessary for each cell to function and is stored in chromosomes. Every time cell division occurs, these chromosomes replicate, and the genetic information they contain is passed onto the daughter cells. With each division, however, the end structure of each chromosome, known as a telomere, is shortened. Hence, telomere length may be an indicator of ageing. “One exception is cancer cells, which can extend telomeres and as a result divide constantly and become immortal,” says one of the study’s authors, biologist Lumír Krejčí.

The researchers focused on a structure known as TERRA and its role in cells. “TERRA, or telomeric RNA, is a long chain of ribonucleic acids that is created when the genetic information contained in telomeres is transcribed. What is its exact purpose was long a mystery”, notes Krejčí. Researchers from EPFL discovered that this structure associated with shortened telomeres creates R-loops. Scientists from MU and FNUSA-ICRC concentrated on studying what factors contribute to TERRA’s attaching to chromosome ends.

They discovered that they are the same factors that contribute to a process known as homologous recombination, in which an undamaged DNA strand is used to repair a damaged section. “We found that a protein named RAD51 is necessary for TERRA to attach to the end of chromosomes. When RAD51 does not function properly, it often leads to cancer. This protein, therefore, may affect the mechanism underlying the extending of telomeres”, says Krejčí.

The researchers plan to further study what cells use these TERRA-loops for and how this mechanism is controlled. “The answer may be critical for overcoming problems with cell division where telomere replication often ends up stopping the replication process. Unsurprisingly, this process is considered critical to the creation of tumours”, states Krejčí, hinting at possible future research.