Cell Cycle Control 
David H. Beach, Ph.D. — Investigator 
Dr. Beach is also Senior Staff Scientist at Cold Spring Harbor Laboratory and Adjunct Associate Professor 
in the Department of Microbiology at the State University of New York at Stony Brook. He received his 
undergraduate degree at the University of Cambridge, followed by a Ph.D. degree at the University of 
Miami, where he worked with Marcus Jacobson. His postdoctoral studies were done with Sydney Shall at 
the University of Sussex and with Amar Klar at Cold Spring Harbor Laboratory. 
THE division of one cell into two, generally 
known as the cell division cycle, is among the 
most basic of biological processes. The underly- 
ing molecular pathways that regulate and elfect 
the cell cycle are gradually being elucidated by a 
combination of genetic, biochemical, and cell bi- 
ological studies. 
The two key events in the cell cycle are the 
replication of nuclear DNA, which occurs during 
the S phase, and cell division or mitosis, often 
referred to as M phase. Genetic studies, using the 
fission yeast, a single-celled organism, have re- 
vealed that both the S and M phases of the cell 
cycle are regulated by a single enzyme. This is a 
protein kinase (which transfers phosphate from 
ATP to a target substrate, altering the substrate's 
biological properties) of which the catalytic sub- 
unit is called cdc2. This enzyme is not only pres- 
ent in yeast cells, but also in those of higher ver- 
tebrates, including humans. 
The cdc2 acts as a multifunctional enzyme by 
virtue of its association with a class of proteins 
called cyclins. Each cyclin, of which many types 
have been identified, binds to cdc2 and confers 
on the protein kinase a particular substrate speci- 
ficity and also targets it to particular cellular lo- 
cations. Different cyclins are synthesized and de- 
graded at particular stages of the cell cycle, 
thereby creating different patterns of cdc2 activ- 
ity during the S and M phases of the division 
cycle. 
The critical cdc2 kinase is not regulated exclu- 
sively by passive association with cyclins, but 
also by its own state of phosphorylation. In partic- 
ular, cdc2 is one of the most heavily tyrosine- 
phosphorylated proteins in actively proliferating 
cells. Tyrosine phosphorylation serves to inacti- 
vate the M-phase form of cdc2 (cdc2/cyclin B), 
and dephosphorylation of the enzyme triggers 
mitosis. 
Our current research is focused on the phenom- 
ena discussed above. In particular, a problem of 
present interest is the mechanism that coordi- 
nates the different phases of the cell cycle. For 
example, why does cell division not occur until 
DNA replication is completed? The genes that 
control such cellular decisions are being 
investigated. 
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