By Cat Holmes
University of Georgia
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 in tumors,
the regulation of cell division goes awry 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
Georgia.
Cat Holmes is a news editor with the University of Georgia
College of Agricultural and Environmental Sciences.
