The Molecular Basis of the Response to Radiation
Abstract
During this three year IDEA Award we have made progress towards all three Technical Objectives. Despite significant efforts we encountered scientific problems isolating novel cDNAs encoding human homologs of yeast DNA damage response genes RAD9 and DUN1 during year 1 and year 2. In contrast, two hybrid screens resulted in the isolation of human homologs of RAD18 and RAD21. Thus, the focus over year 2 and 3 has been the characterization of the human Rad21 protein in mammalian cells and breast cancer samples. Alterations in expression of human Rad21 mRNA and protein in human breast cancer cell lines was detected. Using antibodies produced by this grant we are now determining expression of RAD21 protein in human cancers stratified for aneuploidy. We also demonstrated that Rad21 is cleaved upon induction of the apoptotic pathway (as opposed to DNA damage itself). The cleavage site has been biochemically identified and the characteristics of the cleavage enzyme determined. Cleavage also results in mislocalization of the protein. This cleavage product may play a role in signalling subsequent events in apoptosis or result in aneuploidy which is associated with a poorer prognosis in breast cancer patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA398219
Entities
People
- Sharon E. Plon
Organizations
- Baylor College of Medicine