Telomeres, the beginning(s) of the end. On the Nobel Prize in Physiology or Medicine awarded to Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak

Abstract

The 2009 Nobel Prize for Physiology and Medicine was awarded to Elizabeth H. Blackburn, Jack W. Szostak, and Carol W. Greider for their work on telomeres and telomerase. Telomeres are formed by short DNA sequences repeated in tandem and associated with different proteins. These structures, which are found at the ends of chromosomes, are crucial for maintaining genomic stability by preventing chromosomes from joining with one another. In addition to this essential protective function, telomeres play a vital role in complete DNA end replication. Telomere length is maintained by the enzyme telomerase—a complex made up of RNA and proteins that in humans is active is germinal and embryonic cells but inactive in somatic cells. The absence of telomerase in proliferating cells leads their telomeres to shorten with successive cell divisions. Eventually, the telomeres reach a critically short length that in turn causes massive chromosome instability. This may be the mechanism through which a cell acquires the genetic alternations needed to become malignant. Normally, however, below this critical length, the cells stop dividing and either enter a phase of senescence or an irreversible state of arrest, or mechanisms

are activated for programmed cell death. However, some cells that also carry alterations in cell cycle checkpoint proteins continue replicating, giving rise to uncapped chromosome

ends and thus to a malignant potential.