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Key DNA enzyme can tolerate more mutations than expected

Many of us saw films in school and think of DNA replication -- the duplication of the cell -- as involving a gliding double-helix that breaks apart and smoothly forms new cells as symphonic music swells in the background. But the latest scientific studies show that cell replication is in fact much different, and far more chaotic. There can be a widespread substitution of different elements of the cell, with all sorts of effects. Those effects can be helpful, as in evolutionary change, or bad, as in cells that run amok and form cancer.

A new study from University of Washington researchers shows that a DNA polymerase -- an enzyme -- commonly used for scientific study can tolerate many different mutations and remain functional. The total number of different active mutant forms discovered, 8,000, is apparently the largest library of any polymerase yet known -- and it might be the largest library of any enzyme known.

"This presents whole paradigms of evolution. The active area of these enzymes is one of the most conserved sites in nature -- that nature has ever created. What this says is that the most conserved site in nature is plastic, within the test tube. You can put in all possible mutations," says the co-author, Dr. Lawrence Loeb. Leob is director of The Joseph Gottstein Memorial Cancer Research Laboratory at the University of Washington School of Medicine and is a professor of pathology and biochemistry and director of UW's Medical Scientist Training Program.

The other co-author is Premal Patel, who carried out the studies. He is a medical scientist training program student, in the M.D./Ph.D. program at the University of Washington.

The findings are being published in the May 9 issue of the journal Proceedings of the National Academy of Sciences.

Polymerases are enzymes -- a type of protein -- that can replicate DNA. DNA forms the genes that give us our characteristics.

The polymerase involved is called Taq, the one most often
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Contact: Walter Neary
wneary@u.washington.edu
206-685-3841
University of Washington
8-May-2000


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