Identification and Characterization of Components of the Mitotic Spindle Checkpoint Pathway Using Fission Yeast
Abstract
During anaphase of mitosis, sister chromatids are separated by the mitotic spindle. The spindle assembly checkpoint protects the integrity of the genome by initiating a cell cycle delay if chromosomes are not properly attached to the spindle. Cells lacking a functional spindle checkpoint may gain or lose genetic information, which can cause cell death or predispose cells to cancer. For example, loss of checkpoint function has been observed in human cancer cell lines, and decreased expression of the checkpoint component, hsMAD2, has been demonstrated in human breast cancers. Most human spindle checkpoint components were identified by their similarity to yeast checkpoint proteins that were discovered through genetic screens. Many aspects of spindle checkpoint function are not yet understood, and genetic evidence indicates there are additional checkpoint proteins that have not been identified. This project aims to use genetic screens in fission yeast to identify and characterize novel components of the yeast and animal spindle checkpoint pathways and novel mutant alleles of known yeast spindle checkpoint genes. To date, mutations in three known yeast spindle checkpoint genes and a mutation in a potentially novel component of the yeast checkpoint pathway have been identified. A second genetic screen has been initiated to identify mouse cDNAs which induce a metaphase arrest in fission yeast and may encode spindle checkpoint proteins. The genes identified by these studies will be used to further elucidate the mechanism of spindle checkpoint function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408789
Entities
People
- Sheila Kadura
- Shelley Sazar
Organizations
- Baylor College of Medicine