The Nobel Prize in Physiology or Medicine 2009
Elizabeth H. Blackburn, Carol W. Greider, Jack W. Szostak
Every cell in our bodies contains our entire genome, the blueprint for life, wrapped up within its chromosomes. Each time one of our cells divides to form two new cells, its chromosomes need to be perfectly replicated so that each new cell receives an exact copy of the blueprint. As early as the 1930s, long before the molecular nature of DNA was understood, people such as Hermann Muller and Barbara McClintock had noticed that the very ends of the chromosomes appeared to serve an important protective role. But what these ‘telomeres’, or end parts, actually were remained a mystery.
The first great strides in unravelling telomere function, and understanding how they are maintained, were taken in the early 80s, and it is this work that the 2009 Nobel Prize in Physiology or Medicine rewards. Elizabeth Blackburn used early DNA-sequencing techniques to show that telomeres were made up of short, repeated pieces of DNA. Next, she and Jack Szostak performed an experiment showing that telomeres from one species, a pond-dwelling single-celled organism called tetrahymena, could protect DNA molecules, or mini-chromosomes, from a very distant organism, yeast. The fact that this protective effect was conserved across such vast stretches of evolution told them that they were witnessing a very fundamental biological mechanism in action.
Elizabeth Blackburn and her graduate student Carol Greider then went looking for the mechanism that maintains telomeres, and on Christmas day, 1984, discovered the first evidence for the enzyme telomerase. Combining both protein and RNA components, telomerase is a reverse transcriptase which adds telomere DNA to the ends of molecules using an RNA template. Its discovery presented a solution to one aspect of the puzzling 'end replication problem' which had confounded molecular biologists, who had been unable to understand how DNA could be added to the very tip of one of the two strands of replicating DNA during cell division. By providing, with its RNA, a template for DNA synthesis, telomerase is able to build a platform onto the end of the molecule from which other DNA-synthesizing enzymes can then operate.
This is the 100th time the Nobel Prize in Physiology or Medicine has been awarded, and the first time that any Nobel Prize in the sciences has been awarded to more than one woman. Telomere and telomerase disfunction is now linked with a number of disease states, and therapeutic approaches based upon targeting this system are in development.
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