Role of Sister Chromatid Cohesion in the Apoptotic Response of Normal and Malignment Mammary Cells With Known Aneuploidy
Abstract
Chromosomal segregation abnormalities are a common feature of breast cancer and several studies estimate that approximately 70% of breast cancers demonstrate aneuploidy. Overall, aneuploid tumors have a worse prognosis compared with diploid tumors. Our laboratory has recently isolated the human homolog of the Rad2l cohesin protein (hRad21) as a protein that interacts with the human Cdc34 ubiquitin-conjugating enzyme. The cohesin proteins are required for proper chromosomal segregation in many eukaryotic organisms. Our work led to the unexpected finding that hRad2l undergoes specific cleavage early in apoptosis. Based on this work, we proposed the novel hypothesis that in mammalian cells chromosomal segregation and the apoptotic cell death pathway are directly linked. In this CONCEPT award we have attempted to test this hypothesis. From these studies, it is apparent that cohesin Rad21 may act as an interface between cohesion and cell death, and its cleavage may signal subsequent events of apoptosis, including DNA degradation. It is likely that hRad21 helps maintain chromosomal stability in mammary cells, and its dysregulation results in aberrant cohesion that leads to aneuploidy. This knowledge will be helpful in the derivation of new strategies for the prevention and treatment of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADB274521
Entities
People
- Debananda Pati
Organizations
- Baylor College of Medicine