| Non-Scientific
Abstract In the process of passing through the stages of division of genetic material, the cell has to complete one cell cycle. Progression through the cell
cycle is regulated at many levels in the S. cerevisiae yeast in order to ensure proper segregation of genetic material. Specifically, one of the most
important cell cycle transitions is the point of mitotic exit.Mitotic exit only takes place after chromosomal segregation and mitotic spindle disassembly
and depends upon inactivation of mitotic cyclins.Mitotic cyclin inactivation in turn depends ultimately upon regulation by Cdc14.
Disruption of this transition (as well as other checkpoints in the cell cycle) can lead to cancer.Our interest in this checkpoint leads us to examine
the regulators of Cdc14. Thus far, two pathways have been identified which regulate Cdc14, the Mitotic Exit Network (MEN) and Cdc14
early anaphase release network (FEAR) pathways. In this study we create a screen to look for components of the FEAR pathway; six genes were
identified ó SAC3, FUS3, FBA1, SHE10, NUP57, DML1, and STB4. Further study of these genes is underway to determine if they have a role
in the FEAR pathway.
Abstract Cdc14 regulation is controlled by two pathways, the Mitotic Exit Network (MEN) and Cdc14 early anaphase release network (FEAR) pathways.
The MEN pathway regulates ubiquitin-mediated proteolysis, and in turn mitotic exit, by promoting the release of Cdc14 from its inhibitor.This
release results in the inactivation of mitotic Cdks.The MEN pathway maintains the released state of Cdc14 during anaphase and telophase.The
FEAR pathway actually initiates Cdc14 release from its inhibitor Cfi1/Net1 in the nucleolus during early anaphase. These two networks function
together to control mitotic exit. Crippling of either pathway is detrimental to the cell; crippling of both pathways results in cell inviability.
Therefore, we utilized a yeast strain that has a deletion in the LTE1 gene (a component upstream in the MEN pathway). This yeast strain was
then transformed and screened in order to identify cells which had mutations that were synthetically lethal, implying that they were potentially
a part of the FEAR pathway. Six genes were identified: SAC3, FUS3, FBA1, SHE10, NUP57,DML1, and STB4. Further experimentation is currently
underway to determine the role of these genes in the FEAR pathway. |
