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Study on chromosome ends may aid cancer research

PRINCETON, N.J. -- A Princeton scientist has discovered a mechanism that cells use to control the length of their chromosome ends, a process that is thought to go awry in cancer.

The finding, reported in the August 4 issue of Science by Professor of Molecular Biology Virginia Zakian and colleagues, may provide cancer researchers with clues for designing treatments.

Zakian found a naturally occurring protein that inhibits the activity of another protein, called telomerase, which replicates and lengthens the very ends of chromosomes. The protein, called Pif1p, acts directly on the chromosome ends, called telomeres, to keep the lengthening process in check, Zakian's research group reported.

Researchers have been studying telomerase with great intensity for the past 15 years because it appears to play a central role in the way cells age or become cancerous. Studies have shown that telomerase is present in 90 percent of cancer types, but is absent from most healthy cells. Cancer researchers have thus looked for ways to interfere with telomerase. Zakian's research suggests that mimicking or enhancing the action of Pif1p may be a good way to do so.

Telomerase builds structures called telomeres at the ends of chromosomes, like plastic caps at the ends of shoelaces. In normal conditions, telomeres shorten each time a cell divides, eventually exposing the genetic material and causing the cell to die. In cancer cells, however, telomerase keeps rebuilding the telomere caps, preventing the cell from undergoing its normal aging process.

In 1994, Zakian and collaborator Vincent Schulz reported that Pif1p keeps telomeres from lengthening. It remained unclear, however, how Pif1p accomplished that feat. There are many natural substances that could inhibit telomere lengthening in indirect ways, Zakian said. The new paper shows that Pif1p acts on the telomerase pathway itself and interacts directly with telomeric DNA, a potentially attractive feature for drug de
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Contact: Steven Schultz
sschultz@princeton.edu
609-258-5729
Princeton University
3-Aug-2000


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