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.
