Telomerase

Telomeres are essential structural elements of DNA for the stability of chromosomes and have a high guanine and thymine content, which is highly repetitive (often repeated).

In all vertebrates, for example, the 6 nucleotides TTAGGG are repeated more than 3000 times (up to 4000 times in bred laboratory mice). The folded secondary structure of the telomeres is also important for the stabilization effect. In addition, in some organisms the telomeres are an anchor point to the cell nucleus wall.

With each cell division, the telomeres are shortened as the DNA polymerase can no longer attach to the next strand. If the telomere length falls below a critical minimum of around 4 kbp, the cell can no longer continue to divide, often resulting in cell death or permanent growth arrest ( senescence).

The resulting limitation of the cellular lifespan is known as the tumor suppressor mechanism. The enzyme telomerase, also known as TERT (RNA-protein complex with reverse transcriptase activity), can compensate for the shortening. To do this, it adds G-rich repeat units to the 3'-OH end, the RNA template for which is located in the telomerase itself. The leading-strand then folds over and forms abnormal GG base pairings with itself. From this point, the RNA primase and the DNA polymerase can fill up the lagging strand.

Cells in which this enzyme is active can divide much more frequently than other body cells.

In higher multicellular organisms, however, telomerase is only active in very specific cells, e.g. in the cells of the germ line and in embryonic stem cells (e.g. bone marrow stem cells) or skin cells. More than 90% of tumors reactivate the enzyme telomerase, which is active in the embryonic phase and completes the repetitive sequences of telomeres.

Telomeres are associated with biological processes that are related to the ageing of cells ( cell senescence), but also their immortalization = replicative immortality (and thus also the development of cancer).

The name is derived from the Greek: telomere = end part.

1. Epel ES et al (2004) Accelerated telomeric shortening in response to life stress. Proc Natl Acad Sci 101: 17323-17324
2. McClintock B (1941) The stability of broken ends of chromosomes in Zea mays. Genetics 26: 234-282