The Role of BRCA1 Domains and Motifs in Tumor Suppression
Abstract
The purpose of this research is to classify BRCA1 variants for which cancer association is not known (unclassified variants UCV). To approach this problem we hypothesized that poorly characterized but conserved domains in BRCA1 directly participate in its tumor suppression function. To test this hypothesis we choose a global approach analyzing several BRCA1 domains and point mutants in functions that have previously been attributed to BRCA1: long term survival after irradiation, early G2/M checkpoint, intra S phase checkpoint, and spindle assembly checkpoint. We successfully optimized conditions for expression of full-length BRCA1 mutants in two different cell lines by electroporation and lipofectamine based transfection. We analyzed all the BRCA1 mutants proposed in this application. Our analysis revealed that the coiled-coil domain of BRCA1 is important for the intra-S-phase checkpoint function of BRCA1. We also begin to characterize two conserved motifs of BRCA1: Motif 6 (proposed in this application) and Motif 2 (as a new finding). This will have a significant impact not only to understand BRCA1 role as a tumor suppressor in breast cancer but also to help patients that are carriers of BRCA1 mutation to make informed clinical decisions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2010
- Accession Number
- ADA541878
Entities
People
- Aneliya Velkova
Organizations
- H. Lee Moffitt Cancer Center & Research Institute