Tuesday, 30 November 2010

Telomeres, Telomerase and Cancer

reposted from:

An unusual enzyme called telomerase acts on parts of chromosomes known as telomeres. The enzyme has recently been found in many human tumors and is being eyed as a new target for cancer therapy

telomeres appear as bright ends of chromosomesTELOMERES cap the ends of chromosomes.Image: WIKIMEDIA COMMONS/NATIONAL HUMAN GENOME RESEARCH (user GIAC38)
Editor's note: We are posting the main text of this article from the February 1996 issue of Scientific American for all our readers because the authors have won the 2009 Nobel Prize in Physiology or Medicine. Subscribers to the digital archive may obtain a full PDF version, complete with artwork and captions.
Often in nature things are not what they seem. A rock on the seafloor may be a poisonous fish; a beautiful flower in a garden may be a carnivorous insect lying in wait for prey. This misleading appearance extends to certain components of cells, including chromosomes—the strings of linear DNA that contain the genes. At one time, the DNA at the ends of chromosomes seemed to be static. Yet in most organisms that have been studied, the tips, called telomeres, are actually ever changing; they shorten and lengthen repeatedly.
During the past 15 years, investigation of this unexpected flux has produced a number of surprising discoveries. In particular, it has led to identification of an extraordinary enzyme named telomerase that acts on telomeres and is thought to be required for the maintenance of many human cancers. This last finding has sparked much speculation that drugs able to inhibit the enzyme might combat a wide array of malignancies. The research also opens the possibility that changes in telomere length over time may sometimes play a role in the aging of human cells.
Modern interest in telomeres and telomerase has its roots in experiments carried out in the 1930s by two remarkable geneticists: Barbara McClintock, then at the University of Missouri at Columbia, and Hermann J. Muller, then at the University of Edinburgh. Working separately and with different organisms, both investigators realized that chromosomes bore a special component at their ends that provided stability. Muller coined the term "telomere," from the Greek for "end" (telos ) and "part" ( meros ). McClintock noted that without these end caps, chromosomes stick to one another, undergo structural changes and misbehave in other ways. These activities threaten the survival and faithful replication of chromosomes and, consequently, of the cells housing them.
It was not until the 1970s, however, that the precise makeup of the telomere was determined. In 1978 one of us (Blackburn), then working with Joseph G. Gall of Yale University, found that the telomeres in Tetrahymena, a ciliated, single-cell pond dweller, contained an extremely short, simple sequence of nucleotidesÑ TTGGGG —repeated over and over. (Nucleotides are the building blocks of DNA; they are generally denoted as single letters representing the chemical bases that distinguish one nucleotide from another. The base in nucleotides is thymine; that in Gnucleotides is guanine.) 

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