UGA research team reveals molecular key to cell division

August 22, 2003

Anyone who made it to high school biology has learned about mitosis, or cell division. One cell divides into two, two into four and so forth in a process designed to pass on exact copies of the DNA in chromosomes to daughter cells. New research, by a University of Georgia team, shows how the genes that control this process are regulated.

The study is important for cancer research because the regulation of cell division goes awry in tumors and normal cell growth and behavior are lost. Understanding how normal cell division is regulated will allow scientists to identify potential targets for cancer therapeutics, said Stephen Dalton, the molecular geneticist who led the UGA team.

"This is fundamental molecular cancer research," Dalton said. "One major problem in cancer is mis-segregation, [when the cell's] ability to equally divide chromosomes is lost. One [daughter] cell might get too much genetic information and the other too little.

"This is why many tumors have unbalanced genetic makeup," he said. " The cells lose the ability to accurately segregate their chromosomes because control mechanisms, known as checkpoint controls, are lost."

Dalton worked with Bruce Kemp, deputy director of St. Vincent's Institute for Medical Research in Melbourne, Australia and UGA graduate student Cameron McLean.

Using Brewer's yeast (Saccharomyces cerevisiae) as their model system, the group found that molecules called cyclin-dependent kinases drive the mitosis process. More than 30 genes are switched on at the beginning of the process and switched off after chromosome segregation is complete.

"The yeast is easily manipulated genetically," Dalton said. "And because the mechanisms of cell division are conserved between yeast and humans, the observations we make in yeast, in general, are applicable to humans."

Now, Dalton and his team have turned their attention from yeast to human cells. They are focusing primarily on a group of molecules that have been implicated in many tumors. Collectively, these genes are known as oncogenes and tumor suppressor genes.

"Our work is now focusing on how some of these initial observations in yeast can be applied to understanding molecular control of cell division in human cells," Dalton said, "and how that can be applied to understanding cancer."

The researchers have already made some novel observations about how the cyclin-dependent protein kinases function in human cells. Their findings will be published soon in a separate report.

"We've identified some new mechanisms by which oncogenes and tumor suppressor genes are controlled," Dalton said. "Over the next year, I think we'll get a clear idea of new roles these molecules play in early cell development and then try to fit the pieces together to see how they may influence cell behavior in the context of cancer.

"We've made some observations which fly in the face of the [scientific] literature," he said. "It's going to be quite controversial but very exciting. It's going to have some strong implications for the role these molecules play in cancer development."

The paper outlining the initial research with yeast was published in the July 15 issue of Genes and Development.

A geneticist of international renown, Dalton joined the faculty of the UGA College of Agricultural and Environmental Sciences in January. He is a Georgia Research Alliance Eminent Scholar, a Georgia Cancer Coalition Distinguished Cancer Scientists and a consultant for BresaGen, a cell therapy biotech company in Athens.
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University of Georgia

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