Structural Studies of the BRCA1-Associated Human SWI/SNF Complex
Abstract
Mutations in the tumor suppressor gene, BRCA 1 account for 45% of families with a high incidence of breast cancer and the majority of families with high incidences of both breast and ovarian cancers. Recent data has shown BRCA1 to be associated to be associated with a human SWI/SNF complex, serving to link breast cancer to chromatin remodeling (3). Current evidence points to the idea that BRCAl works through SWI/SNF; therefore a molecular understanding of the SWI/SNF complex and other human chromatin remodeling complexes will offer insight into the biology of BRCA1. The central catalytic ATPase subunit of SWI/SNF is BRG1; the central catalytic subunit of a related human chromatin remodeling complex, NURF, is SNP2H. Initially, crystallization and X-ray structural determination of the core ATPase domain, in addition to the full-length proteins was undertaken unsuccessfully. The core domains and the full-length proteins behave poorly in solution and proved unsuitable for formation of successful crystals. Currently, purification of the entire SWI/SNF and NURF complexes, as well as functional cores of these complexes is underway. This will alleviate the stability problems, and offer more structural and mechanistic insight into how chromatin remodeling complexes interact with BRCAl.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA417022
Entities
People
- Marc Holbert
Organizations
- University of Pennsylvania