Another mechanism of immortality: alternative telomere lengthening

Details of the alternative "mechanism of immortality" of cancer are revealedKirill Stasevich, Compulenta
Cancer cells achieve immortality by preserving the terminal fragments of chromosomes – telomeres.

Many tumors use the enzyme telomerase for this, but there are also those that follow a fundamentally different path. Researchers have found out how these mechanisms differ.

Any eukaryotic cell has a certain maximum number of divisions, called the Hayflick limit: on average, after 50 divisions, the cell dies, aging as it approaches this milestone. The exceptions are immortal cells: stem cells, sex cells and cancer cells.

The mechanism of cancer immortality has long occupied the minds of scientists. If they managed to mess it up, the cancer problem would disappear. Approximately 90% of malignant tumors use the enzyme telomerase for immortality. The restriction on the number of divisions is due to the fact that the machine copying DNA, with each division, slightly under-reads the reproduced molecule. The end zones of chromosomes that are not read during divisions are called telomeres, their size determines the number of cell divisions. But there is an enzyme telomerase, which is able to complete telomeres – and therefore prolong the life of the cell.

Despite the "popularity" of telomerase, there is another mechanism of immortality that tumor cells use: it is called alternative telomere elongation. Here, too, telomeres are lengthened, but in a different way – using a complex homologous recombination reaction. DNA in the cells of our body exists in two identical copies, and if one molecule is damaged, then the damaged area can be transplanted from a paired chromosome: this is called homologous recombination, the exchange of fragments between paired DNA.

Scheme of "normal" recombination between two chromosomes,
accompanying the formation of germ cells (figure Magistra Learning Co).

So cancer cells have learned to restore telomeres by copying DNA due to such recombination.

Scientists from the Salk Institute for Biological Research (USA) tried to find out the details of this alternative telomere elongation. In mammals, both ends of the DNA chromosome are usually terminated by a long section rich in guanine (G). But in cancer cells using an alternative mechanism, chromosomal telomeres carried ends enriched with cytosine (C). About half of the telomeres of tumors with an alternative elongation of these telomeres carried the C-end. This is hundreds of times higher than the occurrence of the same C-sequence in normal cells.

In addition, the C-ends of telomeres were almost not detected among cancer cells using telomerase. But at the same time, according to the head of research Jan Karlseder, such ends of chromosomes are found in roundworms. Two proteins bind to the C- and G-ends of DNA in worms, and if the partner protein is removed from the C-end, then the animal cells will begin to show the features of cancer degeneration.

The full results of the work under consideration (Liana Oganesian, Jan Karlseder // Mammalian 5' C-Rich Telomeric Overhangs Are a Mark of Recombination-Dependent Telomere Maintenance) can be read in the journal Molecular Cell.

As scientists say, tumor cells in which telomerase activity is suppressed often survive anyway and continue to divide due to the transition to alternative elongation of telomeric sites. Thus, it would be good for people to learn how to work on both mechanisms at once. Who knows, maybe the protein of roundworms, which binds to the C-terminal fragments of chromosomes, will help researchers in the fight against cancer...

Prepared based on the materials of PhysOrg: A new ending to an old 'tail'.

Portal "Eternal youth" http://vechnayamolodost.ru25.04.2011