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

Hum Mol Genet. 2001 Nov 1;10(23):2651-60. doi: 10.1093/hmg/10.23.2651.

Abstract

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 / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone
  • DNA Helicases
  • DNA-Binding Proteins*
  • Fanconi Anemia Complementation Group A Protein
  • Gene Expression
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • FANCA protein, human
  • Fanconi Anemia Complementation Group A Protein
  • HSP70 Heat-Shock Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Proteins
  • SMARCC1 protein, human
  • SMARCC2 protein, human
  • SWI1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Smarcc1 protein, mouse
  • Transcription Factors
  • glucose-regulated proteins
  • SMARCA4 protein, human
  • Smarca4 protein, mouse
  • DNA Helicases