Journal Article

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

Tetsuya Otsuki, Yusuke Furukawa, Keiko Ikeda, Hitoshi Endo, Takayuki Yamashita, Azusa Shinohara, Akihiko Iwamatsu, Keiya Ozawa and Johnson M. Liu

in Human Molecular Genetics

Volume 10, issue 23, pages 2651-2660
Published in print November 2001 | ISSN: 0964-6906
Published online November 2001 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/10.23.2651
Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex

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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.

Journal Article.  6996 words.  Illustrated.

Subjects: Genetics and Genomics

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