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Scientists decipher "fail-safe" system that limits gene copying in cells

Our cells constantly flirt with disaster: Before each division, they duplicate hundreds -- often thousands -- of DNA snippets from each chromosome. But if any snippet gets copied twice, the daughter cells will get faulty instructions and may start a buildup of errors that can cause cancer generations hence.

Scientists at the University of California, San Francisco have deciphered the long-puzzling process by which every cell regularly averts these dangers by shutting down the gene copying process as soon as one complete copy is made.

The discovery, published in the journal Nature, involves a fail-safe system of overlapping controls requiring that three separate chemical processes be reversed before the genes can be re-copied - a highly unlikely series of events, and therefore a near-perfect protection.

The molecular-level finding was made by studying the cell cycle in common brewer's yeast, an organism that has proved a powerful model for understanding how human cells function in normal and diseased states. While some of the details may differ in humans, the basic pattern of overlapping controls and the strategies used to carry them out are expected to be similar, the researchers say.

Since, as the scientists finally found, cells use three or more separate strategies to avoid over-copying genes, determining just how the process worked has proved elusive.

"We knew of several potential ways the cell machinery might prevent inappropriate re-replication, but we were repeatedly frustrated in attempts to show that any of them were actually involved," said Joachim Li, PhD, UCSF assistant professor of microbiology and immunology and senior author on the Nature paper. "We would experimentally de-activate one mechanism after another and find no effect. This is not the kind of result that helps convince granting agencies you are on the right track."

"We eventually demonstrated that not one or two, but at least three dis
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
27-Jun-2001


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