Nature's Exquisite Scalpels

For 15 years, Rosenberg and the scientists he works with at his University of Pittsburgh laboratory have studied the DNA-recognition mechanisms of a protein called Eco RI endonuclease. Eco RI is one among a class of enzymes, called restriction enzymes, that protect the DNA in bacterial cells by attacking DNA brought in by viruses and other foreign agents. Restriction enzymes haven't yet been isolated in human cells, but they are nevertheless of paramount practical importance because of their role in DNA analysis and genetic engineering.

"Eco RI is one of the most frequently used in what's called recombinant DNA technology," says Rosenberg, "or in the jargon 'cloning.' These enzymes recognize a particular sequence of bases of DNA and cut the DNA at those sites, breaking it into well-defined pieces that can be put back together in new combinations. Eco RI is the prototype, the first one of these enzymes to be understood and the first one used in this technology."

Largely as a result of Rosenberg's in-depth research on Eco RI, it is the paradigm example of these "exquisitely precise scalpels," as Stanford's Lubert Stryker calls restriction enzymes (in his textbook Biochemistry). "With Eco RI," explains Rosenberg, "we're trying to really get at the basic recognition process. One of the most intriguing questions in molecular biology today is whether general recognition principles will emerge from the details of these individual recognition mechanisms."

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