Our research is focused on how a conserved family
of cell cycle regulatory protein complexes, called
cyclin-dependent kinases (Cdks), coordinate duplication
and segregation events during the cell cycle. We combine
powerful genetic, genomic, molecular, and cellular
approaches in budding yeast.
The yeast centrosome, called a spindle pole body
(SPB), directs the formation of a bipolar spindle
that is essential for the faithful segregation of
chromosomes at mitosis. We have found that disruption
of specific Cdk activities leads to uncontrolled duplication
of SPBs. We have also shown that the amplification
of SPBs can lead to the mis-segregation of chromosomes,
a phenotype commonly observed in tumor cells. Similarly,
we have observed that cells disrupted for specific
cyclin activities undergo multiple rounds of DNA replication
in the absence of mitosis, giving rise to polyploid
cells. As we have seen for SPB duplication, Cdk activities
are also essential for preventing the re-initiation
of DNA replication until the completion of mitosis.
Our work has also suggested the existence of an independent
cell cycle oscillator. In somatic cells and yeast,
checkpoint controls insure that the initiation of
cell cycle events is dependent on the completion of
the preceding events. However, we have observed the
periodic activation of early cell cycle events in
yeast cells where cell cycle progression is halted.
Several G1 events were initiated on schedule in cells
lacking Cdk activities, suggesting that a Cdk-independent
oscillator may time the initiation of early cell cycle
events. One goal of the lab is to identify the components
and characterize the functions of this novel oscillator.
Graduate students will have the opportunity to investigate
various aspects of the regulation of SPB duplication
and DNA replication by cyclin-dependent kinases. Opportunities
also exist to characterize the components and activities
of the independent cell cycle oscillator.
