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'Genetic network' guards against lethal DNA damage

The discovery in yeast cells of a genetic network that guards against lethal DNA damage is a first step in the creation of a database of disease-causing combinations of mutated human genes, according to researchers at The Johns Hopkins University School of Medicine led by Jef. D. Boeke, Ph.D. In a report in the March 10 issue of Cell, the Hopkins team described a genetic network that is necessary for ensuring genomic stability in yeast. This study also identified previously unrecognized genes critical for maintaining DNA integrity and novel functions for well-known genes.

"A lot of human diseases are caused by multiple gene mutations that are difficult to identify," said Boeke, who is a professor of molecular biology and genetics and director of the High Throughput Biology Center at the Hopkins School of Medicine.

The yeast cell is an excellent model for this kind of study because 25 percent of human disease genes are also found in yeast, according to Boeke. Therefore, the discovery of this network of genes could help to identify mutations whose combined deleterious effects cause human diseases, including cancer and neurodegeneration, as well as aging.

"The interactions we discovered in yeast could also help researchers select the human versions of these genes suitable as targets for the development of new, more targeted and less toxic cancer therapies," Boeke said.

The goal of the Hopkins study was to identify pairs of genes that, while different, play redundant roles in governing genomic integrity in yeast cells, filling in for each other when one of the genes is mutated or deleted. Such redundancies ensure that each task in the network of biochemical reactions governing DNA stability is accomplished, Boeke noted.

Based on the data from this study, the investigators were able to separate the genes governing the stability of yeast DNA into 16 modules, or mini-pathways of genes, based on these genetic interactions, which are ca
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Source:Johns Hopkins Medical Institutions


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