the story behind telomerase. no caps!

In the early 1900s. Hermann Muller and Barbara McClintock observed an enigmatic structure found at the end of chromosomes that prevented chromosomes from sticking to one another and hence displayed a protective role cytogenetically.
It was only in the 1950s that the process of replication was understood during this time, researchers noticed that the DNA polymerase enzymes that copied the four nucleotide bases could not copy the very end of every one of the two DNA strands. Based on this observation, a chromosome would have to be shortened after every cycle of cell division. Nonetheless, we know for a fact that cell division is an incredibly robust process.

Elizabeth Blackburn while studying the chromosomes of Tetrahymena, a unicellular ciliate organism found the DNA sequence CCCCAA repeated several times at the end of chromosomes. Around the same time, Jack Szostak observed that a linear DNA molecule, a type of minichromosome, is rapidly degraded when introduced into yeast cells. Szostak was introduced to Blackburn's research during a conference in 1980 which is when the pair decided to come up with a phenomenal experiment using their two model organisms.

Blackburn isolated the repetitive CCCCAA sequence from Tetrahymena and collaborated with Szostak to have it coupled into the minichromosomes before having them put back into the yeast cells. The results from such an experiment displayed that the repetitive end associated minichromosomes were protected from degradation. This experiment confirmed that the sequence, now known as the telomere did in fact have protective functions. And the experiment being conducted cross species showed that the mechanism of protection would have to be an undiscovered and conserved one. Further experiments made it evident that telomere DNA with its characteristic sequence is present in most plants and animals, from the amoeba to man.

However, the discovery of there being a fundamental is not where research stops. Carol Grieder, a graduate student under the guidance of Elizabeth Blackburn investigated the formation of this enigmatic telomeric sequence and hypothesized that its presence could be driven enzymatically. It was only on 25th December 1984, Christmas Day when Grieder discovered the signs of enzymatic activity in a cell extract. Naming this enzyme telomerase, and showed that the purified enzyme consists of RNA as well as protein. The RNA component consisted of the CCCCAA sequence and therefore would have to have been the template for which the telomere is built and the protein would in such a situation be involved in the construction work at the chromosome end. It was further confirmed that telomerase extends telomere DNA, providing a platform that enables DNA polymerases to copy the entire length of the chromosome without missing the very end portion.

Research in this area continued and Szostack’s group identified that yeast cells mutated to have gradually shortened telomeres would grow poorly and eventually stop dividing. Blackburn as well when making mutations in the telomerase RNA template observed the same in tetrahymen. This marked the discovery to the reason of cellular ageing- senescence. Grieder’s group showed that senescence due to telomerase inactivation and delay was seen in human cells as well.

Hence, for their work on solving how chromosomes were copied completely and how they were protected against degradation, Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak were awarded the 2009 Nobel Prize in Physiology or Medicine.