Isolation of Genes Required for the Regulated Separation of Sister Chromatids.
Abstract
Aneuploidy, a change in a cells karyotype involving loss or gain of chromosomes, is a key event in the etiology of breast cancer. Since aneuploidy can result from mitotic non- disjunction, understanding the process of chromosome segregation is greatly important. The purpose of this research has been to identify new proteins that are required for maintaining the fidelity of chromosome segregation. Using budding yeast as an experimental system, we identified strong genetic interactions between RAD23, DDIl, ESP1 and the anaphase regulator PDSl. We determined that Rad23p and Ddilp are essential for a Pdslp- dependent checkpoint system that couples replication with mitosis: mutant rad23 ddil cells become aneuploid when challenged with replication inhibitors. We therefore identified 2 proteins required for the regulation of chromosome segregation in yeast. Both RAD23 and DDIl are highly conserved in human cells, though defects in these genes have not been previously implicated in the generation of aneuploid cells. Knowledge such as this will allow us to define genetic and environmental factors which cause non-disjunction; many of these factors will be critically involved in the etiology of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1998
- Accession Number
- ADA352347
Entities
People
- Cclarke J. Duncan
Organizations
- Scripps Research