The long-term interest of my laboratory is to understand how the
cellular genome is duplicated during the cell cycle. In the
course of growth and division, eukaryotic cells duplicate their
genomes with remarkable fidelity. The precision of this process
depends in large measure upon stringent regulatory mechanisms
that couple DNA replication to cell cycle progression.
Initiation must be triggered at the appropriate time in the cell
cycle at many hundreds or thousands of separate sites (origins
of DNA replication) in the parental chromosomes. However,
initiation must be prevented at these same sites in the newly
synthesized daughter chromosomes. These controls ensure that
each DNA segment in the genome is duplicated in a timely fashion
exactly once each cell cycle. Additionally, DNA replication must
be coordinated with the other events of the cell cycle, such as
mitosis and cell division. This coordination is achieved by
regulatory mechanisms that enforce the strict alternation of DNA
replication and mitosis. F