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Genome-wide screen reveals new tricks of old genes

ells survive but their genetic material gets scrambled."

It's that sometimes-yes-sometimes-no problem that Spencer and her team are trying to figure out, in part because it's interesting biology, but also because genetic instability plays such a big role in the development of cancer in humans. No one knows exactly at what point errors enter the genetic material and aren't fixed, but the intricacies of chromosomes' manipulation during cell division seem a good place to start.

Postdoctoral fellow Cheryl Warren, Ph.D., started the search by screening 5,916 yeast genes -- all at once -- for ones needed for survival in the absence of a gene called ctf4, already known to be a critical component of cohesion. Twenty-six genes popped out of this screen, a type known as "synthetic lethal" since the yeast survive the loss of either one, but not both, genes.

However, the synthetic lethal effect of some, if not many, of the genes from this screen would be due to problems other than faulty cohesion, the researchers knew. "We had to do something else to get a manageable starting point," says Warren.

So, using a technique she developed to identify whether a gene's loss causes the genetic material to become scrambled, Warren tested those 26 genes to see which of them seemed most likely to contribute to genetic instability through their involvement in cohesion. In these experiments, markers were scattered throughout the yeast's genetic material so she could easily tell if pieces of the genome moved or went missing when a gene was knocked out.

Only 17 of the 26 identified genes caused genetic instability when missing from the yeast genome. Fifteen of those genes are involved in double-checking whether newly formed strands of DNA matched the cell's original genetic material and calling in "repairmen" as needed (a process called the "S-phase checkpoint"). The other two genes are part of the machinery previously known to help move the two sets
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
22-Apr-2004


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