Americans Elizabeth Blackburn (University of California San Francisco), Carol Greider (Johns Hopkins School of Medicine) and Jack Szostak (Howard Hughes Medical Centre, Harvard) jointly share the Nobel Prize in Physiology or Medicine 2009 “for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase
” (see Nobelprize.org
Their work focused on how the ends of chromosomes are protected from degradation during replication. Blackburn and Szostak discovered a repeated sequence (TTAGGG) at the end of chromosomes, known as the telomere, in which a single strand of DNA loops back on itself to form a 4-stranded stacked arrangement called a G-quadruplex. This knot-like structure effectively caps the end of the chromosome, preventing degradation of the functional genetic material. In normal cells, as the cell ages, the telomeres shorten and eventually disappear, resulting in uncapped chromosome ends which triggers cell death (apoptosis). This process has been widely linked to systemic aging, and some anti-aging strategies have focused on trying to lengthen the telomeres. Putative G-quadruplex sequences have also been found throughout the genome, and may play an important role in regulating gene expression.
Blackburn and Greider went on to discover the enzyme telomerase, which maintains telomeres and hence keeps cells young and able to divide indefinitely. The enzyme contains an RNA template of the telomeric repeat, which it uses to extend the DNA repeat at the ends of chromosomes. Although most cells do not divide frequently, and hence do not express telomerase, it is active in stem cells and in around 90% of human tumours. As a result, numerous anti-cancer agents - many of which are currently in clinical trials - have been directed at inhibiting the action of this enzyme.
The Nobel committee said that “the discoveries by Blackburn, Greider and Szostak have added a new dimension to our understanding of the cell, shed light on disease mechanisms, and stimulated the development of potential new therapies.”