Molecular Basis of the Response to Radiation
Abstract
This three year IDEA Award with a one year no cost extension has been completed. We have made progress towards all three Technical Objectives. 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 RAD2l and the focus over years 2, 3 and 4 has been the characterization of the human RAD2l protein in mammalian cells and it's degradation in response to DNA damage. Alterations in expression of human RAD2l mRNA and protein in human breast cancer cell lines were detected. We also demonstrated that RAD2l is cleaved upon induction of the apoptotic pathway (as opposed to DNA damage itself). The cleavage site has been biochemically identified, characteristics of the cleavage enzyme determined and cellular localization of the cleaved proteins performed. The carboxy terminal RAD2l cleavage product has a pro-apoptotic effect on murine mammary cells generating a positive feedback loop in apoptosis. A manuscript describing this regulation of the mammalian RAD2l protein has been submitted and is currently under review.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA408686
Entities
People
- Sharon E. Plon
Organizations
- Baylor College of Medicine