Telomeres as the Key to Cancer

The standard modus operandi for modeling human diseases in the mouse: Find an interesting gene, knock it out, and watch what happens. In theory, the approach makes perfect sense, and scientists have obtained countless subtle insights into the complexities of biology because of it. But mice, of course, are not humans, and many investigators have had to hastily rewrite otherwise elegant theories because of mouse data. One reason? Researchers have taken for granted that telomere length matters. But

Jeffrey Perkel

| 9 min read

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Composed of both DNA and protein, telomeres are the specialized caps at the ends of linear chromosomes. The telomere's DNA contains hundreds of repetitions of a simple, short sequence (TTAGGG in humans), synthesized by a highly specialized enzyme called telomerase. From a teleological point of view, telomeres exist to solve the end replication problem, which arises from what Elizabeth Blackburn, professor of biochemistry and biophysics at the University of California, San Francisco, and telomerase's discoverer, calls a "glitch in the way the DNA replication machine is set up." The DNA polymerases that duplicate DNA are incapable of copying the very ends of a linear DNA molecule. To avoid the loss of critical genetic material, the cell caps its DNA with long stretches—10 to 20 kilobases (kb) or so in human cells—of noncoding sequence.

Telomeres have another function, too: their structure helps the cell distinguish the normal end of a linear ...

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