Seattle, WA (10/12/01)- Three biologists share this year's Nobel
Prize in Physiology or Medicine for helping to unlock the secrets of the cell
cycle, findings with broad implications in biology and medicine. Two
British researchers, R. Timothy Hunt and Paul M. Nurse, both at the Imperial
Research Cancer Foundation, will share the prize with Leland H. Hartwell of
the Fred Hutchinson Cancer Research Center in Seattle.
the first phase (G1) the cell grows. When it has reached a certain size
it enters the phase of DNA-synthesis (S) where the chromosomes are duplicated.
During the next phase (G2) the cell prepares itself for division. During
mitosis (M) the chromosomes are separated and segregated to the daughter
cells, which thereby get exactly the same chromosome set up. The cells
are then back in G1 and the cell cycle is completed.
This year's Nobel Laureates discovered mechanisms controlling the cell
cycle. CDK-molecules and cyclins drive the cell from one phase to the
next. The CDK-molecules can be compared with an engine and the cyclins
with a gear box controlling whether the engine will run in the idling
state or drive the cell forward in the cell cycle.
The three scientists each contributed key insights into the molecular processed
that drive the cell division in all eukaryotic organisms, from the lowly yeast
Saccharymyces cerevisiaeto the Homo Sapiens.
More than twenty years ago Dr. Hartwell, began conducting key experiments
with baker's yeast- Saccharymyces cerevisiae- that revealed the genetic
basis of cell division. His work revealed that the basic molecular mechanisms
governing cell division in yeast are identical to those at work in more advanced
organisms. Indeed, thanks to Hartwell, yeast has become the workhorse of molecular
"What Lee did 25 years ago was essentially provide us with a list of all
the important genes involved in controlling cell proliferation. This has proven
to be invaluable in interpreting and using today's gene-sequence data. Second,
Lee provided a logical framework to understand how these genes cooperate and
work together to control cell division. Thus, he was not merely a cataloger
of genes, but he also was able to explain how they worked," notes colleague
James Roberts, MD, Ph.D., a Howard Hughes Medical Institute investigator and
researcher at the Fred Hutchinson Cancer Research Center.
Hartwell identified more than one hundred genes involved in cell cycle control,
known as CDC-genes (cell division cycle genes). His studies of the sensitivity
of yeast cells to irradiation formed the basis for the concept of checkpoint,
i.e. that the cell cycle is arrested when DNA is damaged. This allows the
DNA to repair itself before the cell continues to the next phase of the cycle.
These findings led to important insights into how cancer cells develop.
Using a different type of yeast, Schizzosaccharomyces pombe, British
researcher Dr. Paul Nurse discovered identified, one of the key regulators
of the cell cycle, CDK (cyclin dependent kinase). His work demonstrated that
CDK controls the the cell cycle via the phosphorylation of other proteins.
Another British researcher, Dr. Timothy Hunt, used the Arbacia sea
urchin as a model system to uncover the existence of cyclin molecules.
These proteins are formed and degraded during each cell cycle. The levels
of these proteins vary periodically during the cell cycle. The cyclins bind
to the CDK molecules, regulating the activity of CDK activity, selecting the
proteins to be phosphorylated.
Taken together, the work of the three biologists went a long way to explaining
the basic molecular mechanisms involved in the regulation of the cell cycle.
This research in turn opened the way to a better understanding of the chromosomal
aberrations that result from defects in cell cycle control, resulting in cancer
cells. Cancer researchers now know that genes for CDK-molecules and cyclins
can function as oncogenes. In a different setting, CDK-molecules and cyclins
collaborate with the products of tumor suppressor genes during the cell cycle.
New cancer diagnostic tools based on this research are now entering the clinic.
Clinical studies are also now getting underway using drugs that have been
designed to inhibit CDK-molecules as a potential treatment for cancer.