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Discovery of cellular 'switch' may provide new means of triggering cell death, treating disease
Date:3/11/2010

r RNA molecules -- which carry DNA's genetic messages from the nucleus of cells to make specific proteins in cell cytoplasm -- and silence their activity, said Xue. But when caspase comes in contact with Dicer, it takes away Dicer's ability to cleave RNA and it replaces it with the ability to snip up and destroy DNA-laden chromosomes.

The experiments were undertaken on a common, eyelash-sized nematode known as Caenorhabditis elegans, a popular laboratory organism for genetic and biomedical experiments. The study of cell death in C. elegans is providing critical information to scientists trying to understand cell death mechanisms in humans and identify ways to combat human diseases caused by "inappropriate apoptosis," Xue said.

"There are many enzymes whose job it is to cut RNA, and many unrelated enzymes whose job it is to cut DNA," said CU-Boulder MCD Biology Department Chair Tom Blumenthal, who studies RNA processing in C. elegans and who was not involved in the study. "But this is the first time that anyone has shown that it is possible to cleave an RNA-cutter enzyme and thereby convert it to a DNA-cutter enzyme."

As part of the study, the team "knocked out" the C. elegans gene that encodes the Dicer enzyme. The removal of the gene compromised the apoptosis process and blocked the fragmentation of chromosomes, said Xue.

Genetic studies of C. elegans have identified many genes that are important for the five sequential steps of programmed cell death, Xue said. They include the specification of which cells should die, the activation of the cell death program, the onset of the killing process, the engulfment of cell "corpses" and the degradation of cellular debris, said Xue.

"Our findings initially seemed too good to be true," said Xue, who said the team has been working on the project for five years. "We wound up looking at the results from a number of angles, including genetics
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Contact: Ding Xue
ding.xue@colorado.edu
303-492-0271
University of Colorado at Boulder
Source:Eurekalert  

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