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Scientists identify 'master' molecule that controls action of many genes

UCSF-led scientists have identified the first "master" molecule in the cell nucleus that controls the action of hundreds of different genes at once through its action on enzymes. The broad-acting molecule affects enzymes that restructure chromosomes, exposing genes to proteins that can then trigger key gene processes, including the start of protein production and copying and repairing of genes.

The molecule's broad effect on a number of genes may allow organisms including humans -- to respond quickly to stress, the scientists say. The research finding is based on studies of yeast, but the same molecule is present in humans and all higher organisms. Mutations that affect enzymes involved in chromosome restructuring have been linked to human cancers.

The study is published by SCIENCE through its Science Express web site. The paper will appear in a later print issue of SCIENCE.

"Many enzymes have been identified that modify chromosome structure and trigger gene transcription, but this is the first example of a molecule that regulates these restructuring enzymes and can affect many, many genes at once," said Erin O'Shea, PhD, a Howard Hughes Medical Institute Investigator and professor of biochemistry at UCSF. O'Shea is senior author on the paper. (Transcription is the first key gene process that ultimately leads to the synthesis of new proteins.)

"This molecule's action might allow the cell to regulate the activity of a number of genes in response to stress," O'Shea said. "Chromosome-altering enzymes control important genes in cells. Mutations in the corresponding human enzymes predispose people to a variety of cancers."

The SCIENCE paper clarifies how one molecule, known as inositol polyphosphate, regulates two chromosome-modifying enzymes inside yeast cells. In the same issue of SCIENCE, a team led by researchers at the National Institutes of Health reports results from test tube experiments also showing the molecule controls
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
18-Nov-2002


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