Since then, scientists have characterized the telomeres in a host of creatures, including animals, plants and microorganisms. As is true of Tetrahymena, virtually all telomeres—including those of mice, humans and other vertebrates— contain repeated short subunits often rich in T and G nucleotides [see "The Human Telomere," by Robert K. Moyzis; SCIENTIFIC AMERICAN, August 1991]. For instance, human and mouse telomeres feature the sequence TTAGGG; those of roundworms feature TTAGGC. ( A stands for adenine, C for cytosine.)
The telomerase enzyme that is the object of so much attention today was found when comparisons of telomere length suggested such an enzyme could resolve a long-standing puzzle in biology. By the early 1980s investigations had revealed that, for some reason, the number of repeated subunits in telomeres differs between organisms and even between different cells in the same organism. Moreover, the number can fluctuate in a given cell over time. (Every species, however, has a characteristic average. In Tetrahymena, the average telomere has 70 repeats; in humans, 2,000.) The observed heterogeneity led Blackburn, who had moved to the University of California at Berkeley, Jack W. Szostak of Harvard University and Janis Shampay of Berkeley to propose a new solution to what has been called the end-replication problem.
The problem has to do with the fact that cells must replicate their genes accurately whenever they divide, so that each so-called daughter cell receives a complete set. Without a full set of genes, a daughter cell may malfunction and die. (Genes are those sequences of nucleotides that give rise to proteins and RNA, the molecules that carry out most cellular functions. The genes in a chromosome are scattered throughout the large expanse of DNA that is bounded by the chromosome's two telomeres.)
In 1972 James D. Watson, working at both Harvard and Cold Spring Harbor Laboratory, noted that DNA polymerases, the enzymes that replicate DNA, could not copy linear chromosomes all the way to the tip. Hence, the replication machinery had to leave a small region at the end (a piece of the telomere) uncopied. In theory, if cells had no way to compensate for this quirk, chromosomes would shorten with each round of cell division. Eventually, the erosion would eliminate the telomeres and critical genes in some generation of the cells. These cells would thus perish, spelling the end of that cellular lineage. Clearly, all single-cell species subject to such shortening manage to counteract it, or they would have vanished long ago. So do germ-line cells (such as the precursors of sperm and eggs), which perpetuate the species in multicellular organisms. But how do such cells protect their telomeres?
For Blackburn, Szostak and Shampay, the observed fluctuations in telomere length were a sign that cells attempt to maintain telomeres at a roughly constant size. Yes, telomeres do shorten during cell division, but they are also lengthened by the attachment of newly synthesized telomeric subunits. The researchers suspected that the source of these additional repeats was some undiscovered enzyme capable of a trick that standard DNA polymerases could not perform.
When cells replicate their chromosomes, which consist of two strands of DNA twisted around each other, they begin by separating the double helix. The polymerases use each of these "parent" strands as a template for constructing a new partner. The special enzyme the workers envisioned would be able to build extensions to single strands of DNA from scratch, without benefit of an existing DNA template.
In 1984 the two of us, working in Blackburn's laboratory at Berkeley, set out to discover whether this putative telomere-lengthening enzyme—telomerase —actually existed. To our delight, we found it did. When we mixed synthetic telomeres with extracts of Tetrahymena cells, the telomeres gained added subunits, just as would be expected if the proposed enzyme were present.
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6 Comments
Add CommentThis is the type of research we are missing in todays world. The pure quest for knowledge instead of profit. They deserved this prize and more.
Reply | Report Abuse | Link to thisKerry,
Reply | Report Abuse | Link to thisYou are being a bit rash or maiybe even uninformed with your statement that "this is type of research we are missing in todays world". There are several research programs at centers, such as the genome labs at Bethesda and in various departments at universities such as Duke where "the quest for knowledge" in the regulation of chromosome replication is on-going. Please note that these nobel lauerates remain in the USA because of our vigorous support of basic research.
Tetrahymena rules again as the queen of free living cells !!
Reply | Report Abuse | Link to thisThis study surely added a new dimension to our understanding of the cell, shed light on disease mechanisms, and stimulated the development of potential new therapies.
Reply | Report Abuse | Link to thisTELOMERASE
Reply | Report Abuse | Link to thisPlease let me know how I can get my sister into this therapy. She has been suffering from cancer for the last 30 years!! She is valiantly fighting for her life and I pray this my help her. Please let me know. Thank you for your wonderful work.
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