24 September 2014

Telomerase activity switch

Scientists at the Salk Institute for Biological Research, working under the guidance of Professor Vicki Lundblad, have demonstrated that the telomerase molecule has a "switch" of activity, the study of which can reveal to a person the secret of healthy aging.

Human tissues and organs are constantly being updated due to dividing cells. However, the number of divisions for most cells is limited, since each division cycle is accompanied by shortening of telomeres – the end sections that ensure the integrity of chromosomes. Shortening of telomeres to a critical length means that the cell reaches the phase of physiological aging and loses the ability to divide. However, some cells (stem and malignant) overcome this barrier with the help of the telomerase enzyme, which restores the length of telomeres and gives them the ability to divide indefinitely.

Based on the results of earlier studies, experts concluded that after assembling the enzyme subunits inside the cell, telomerase retains its activity for a long time. However, the authors unexpectedly refuted this statement.

In experiments on yeast Saccharomyces cerevisiae, Professor Landblad's group has already uncovered a number of mechanisms of telomerase functioning, thus facilitating the process of studying the human version of this enzyme. This was helped by a strategy of their own development, which allows them to observe each of the components of the enzymatic complex in the process of cell growth and division with very high resolution.

Each time a cell divides, its genome doubles. The authors' observations showed that during the DNA doubling process, telomerase is represented by a "precursor complex" represented by three of the four telomerase subunits: Est1, TLC1 and Est2. The fourth subunit – Est3 – joins it only after the completion of genome doubling. As a result, a full-fledged active telomerase complex is formed, capable of restoring the ends of telomeres shortened during division.

However, as it turned out, after performing its function, telomerase quickly decays due to the separation of another subunit, Est2. The authors suggest that this mechanism performs the function of maximally reducing the level of telomerase activity in cells. Despite the fact that shortening the telomeres of normal cells can aggravate the aging process, cancer cells, on the contrary, use telomerase to ensure their unregulated division.

The authors believe that the study of the mechanisms of activation and deactivation of telomerase revealed by them will help to develop manipulations that in the future will allow slowing down the process of shortening telomeres and, possibly, will help in the fight against age-related diseases.

The article by Timothy M. Tucey and Victoria Lundblad Regulated assembly and disassembly of the yeast telomerase quaternary complex is published in the journal Genes and Development.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Salk Institute for Biological Studies:
Scientists discover an on/off switch for aging cells.


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