Researchers identify protein important for beginning gene-activation process

Researchers at Penn State have identified the single protein that initiates the gene-activation process in yeast when it marks the start of a gene and allows the transcription process to begin. An important step toward a better understanding of the gene-activation process, the discovery also promises potential applications in the effort to combat diseases such as cancer and leukemia because a comparable protein exists in humans.

The research findings will be published in the 22 June 2001 edition of Science.

"We had known that proteins were attracted to the end of a gene in order to start the process, but the question was which protein did the work," says Jerry Workman, the Paul Berg Professor of Biochemistry at Penn State and an associate investigator with the Howard Hughes Medical Institute. "What we found was an interesting protein, Tra1, that has a human homolog, Trrap, which has been implicated as an important factor in the transformation of cells into cancer cells by several oncagene products, proteins that are active in a number of tumors."

Using an interdisciplinary approachcombining biochemical, "crosslinking," and genetic methodsthe researchers studied NuA4 and SAGA, two protein complexes of a type known as histone acetyltransferase complexes, or HATs. Gene activation begins when HATs attach to a single gene on a DNA molecule. Although many different proteins comprise SAGA and NuA4, they share just one protein, Tra1.

With a mixture of experimental methodstraditional biochemical and genetic experiments as well as a "crosslinking" experiment, where the use of a purified complex helped distinguish which protein among the many was being recognized by the genethe researchers showed that the two different complexes were recruited to the gene because they shared that same Tra1 subunit.

According to Workman, the combined approaches and the collaboration with Song Tan, assistant professor of biochemistr

Contact: Steve Sampsell
Penn State

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