Nobel Prize Awarded to Investigators of Telomeres and Telomerase

The 2009 Nobel Prize in Physiology or Medicine was awarded to three investigators who showed how chromosomes are completely copied during cell divisions and how they are protected against degradation.

Dr. Elizabeth Blackburn, professor of biology and physiology at the University of California, San Francisco (USA), and Dr. Jack Szostak, professor of genetics at Massachusetts General Hospital (Boston, USA) discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Dr. Carol Greider, professor of molecular biology and genetics at Johns Hopkins University (Baltimore, MD, USA) and Dr. Blackburn identified telomerase, the enzyme that makes telomere DNA.

These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase.

Telomeres are extensions of the linear, double-stranded DNA molecules of which chromosomes are composed, and are found at each end of both of the chromosomal strands. In most eukaryotes telomeres consist of several thousand repeats of the specific nucleotide sequence TTAGGG and occur in organisms ranging from slime molds to humans.

The telomeres become shorter each time a cell divides. When the telomeres reach a specific short length, they signal the cell to stop dividing. Therefore, cellular aging, as marked by telomere shortening, is not based on the passage of time but rather on rounds of DNA replication.

Cancer cells escape telomere loss by switching on the gene that encodes for the enzyme telomerase. This enzyme is a reverse transcriptase that has an RNA template and a catalytic portion. At each round of DNA replication, telomerase adds onto the existing telomeres the nucleotides that would otherwise have been lost, thus maintaining a constant telomere length. Thus, telomerase acts as an "immortalizing" enzyme. In addition, it has several associated proteins whose roles are still under investigation.

Using the TRAP assay (telomeric repeat amplification protocol), it has been found that about 90% of all human tumors produce telomerase, whereas the only normal adult somatic cells that produce telomerase are stem cell populations found, for example, in skin, the hematopoietic system, germ cells, and gut epithelia.

The presence or absence of telomerase is the most specific property that distinguishes cancer cells from normal cells. This difference is currently under investigation as a diagnostic tool. If a chemical could be found to interfere with telomerase activity in cancer cells, an effective control of this disease might be found. Several candidate substances have been identified and are undergoing extensive studies in animals.

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University of California, San Francisco
Massachusetts General Hospital
Johns Hopkins University