Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex.

Fanconi anemia (FA) is a genetic disorder that predisposes to hematopoietic failure, birth defects and cancer. We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase activity. FANCA was ...
demonstrated to associate with the endogenous SWI/SNF complex. We also found a significant increase in the molecular chaperone, glucose-regulated protein 94 (GRP94) among BRG1-associated factors isolated from a FANCA-mutant cell line, which was not seen in either a normal control cell line or the mutant line complemented by wild-type FANCA. Despite this specific difference, FANCA did not appear to be absolutely required for in vitro chromatin remodeling. Finally, we demonstrated co-localization in the nucleus between transfected FANCA and BRG1. The physiological action of FANCA on the SWI/SNF complex remains to be clarified, but our work suggests that FANCA may recruit the SWI/SNF complex to target genes, thereby enabling coupled nuclear functions such as transcription and DNA repair.
Mesh Terms:
Cell Line, Cell Nucleus, Chromatin, Chromosomal Proteins, Non-Histone, DNA Helicases, DNA-Binding Proteins, Fanconi Anemia Complementation Group A Protein, Gene Expression, HSP70 Heat-Shock Proteins, Hela Cells, Humans, Immunoblotting, Membrane Proteins, Microscopy, Confocal, Mutation, Nuclear Proteins, Precipitin Tests, Protein Binding, Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors, Tumor Cells, Cultured, Two-Hybrid System Techniques
Hum. Mol. Genet.
Date: Nov. 01, 2001
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