| Non-Scientific Abstract Cancer, a leading cause of death in the United
States, is caused by abnormal cell division. In order to find a cure for this overproduction of
tumorous cells, it is essential to understand the pathways of regulatory networks involved in
chromosome segregation during mitosis. Two pathways, the Mitotic Exit Network (MEN) and Cdc Fourteen
Early Release network (FEAR), regulate exit from mitosis.When both are blocked in the spo12Δ lte1Δ
double mutant, cells are unable to exit from mitosis.We identified a loss of function mutation in
the KIN4 gene that suppresses the lethality of this double mutant. The phenotype suggests that
KIN4 may negatively regulate exit from mitosis.
Abstract
Abnormal cell division during mitosis leads to overproduction of tumorous cells resulting in
cancer, a leading cause of death in the United States.Mitosis, the process of chromosome segregation,
is a tightly regulated process. To discover a cure for cancer, it is essential to understand the
pathways of regulatory networks involved in chromosome segregation during mitosis.Two pathways, the
Mitotic Exit Network (MEN) and Cdc Fourteen Early Release network (FEAR), regulate exit from mitosis.
In order to identify additional regulators of the FEAR and MEN networks, we are experimenting with the
possibility of a suppressor mutation in the MEN or FEAR pathways that can rescue the synthetic
lethality of spo12Δ lte1Δ.When both pathways are blocked in the spo12Δ lte1Δ double mutant, cells
are unable to exit from mitosis.We report here the identification of the KIN4 gene as a
candidate gene that, when mutated, will suppress the synthetic lethality of spo12Δ lte1Δ
mutants. Isolation of this gene may reveal whether or not it negatively regulates either or both of
the MEN and FEAR pathways. Since little is known about KIN4 other than its function as a
protein kinase, further experiments are needed to determine whether or not KIN4 participates in
localization of Cdc14 as a negative regulator of the MEN or FEAR pathways. |
