Structural Studies of the BRCA1-Associated Human SWI/SNF Complex
Abstract
Mutations in the tumor suppressor gene, BRCA1 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 he associated with a human SW/SNF complex, saving to link breast cancer to chromatin remodeling (3). Current evidence points to the idea that BRCA1 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 AIPase submit of SWI/SNF is BRC1; the central catalytic subunit of a related human chromatin remodeling complex, NURF, is SNF2H. initially, crystallization and Xray structural determination of the core AThase domain, in addition to the fill-length proteins was undersaken unsuccessftilly. Initial purification and expression of a SWI/SNF tinctional core and the SNF2H contaiaing NURF complex were also unsuccexsftil. The conserved core ATPase domain was identified in two more primitive organisms. A recombinant homologous AThase domain was expressed, purified, and small needle-like crystals were grown. Optimization and refinement of these initial crystals is underway to obtain Xray diffraction quality crystals for structral determination of this homologous archacal ATPase domain.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425716
Entities
People
- Marc A. Holbert
Organizations
- University of Pennsylvania