Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex
Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex
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DOI：
10.1093/hmg/10.23.2651
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发表时间：
2001-11-01
影响因子：
3.5
通讯作者：
Liu, JM
中科院分区：
文献类型：
--
作者：
Otsuki, T;Furukawa, Y;Liu, JM
范可尼贫血（FA）是一种遗传性疾病，容易导致造血功能衰竭，出生缺陷和癌症。我们鉴定了FA蛋白、FANCA和brm相关基因1（BRG 1）产物之间的相互作用。BRG 1是SWI/SNF复合物的一个亚基，通过DNA依赖性ATP酶活性重塑染色质结构。FANCA被证明与内源性SWI/SNF复合物相关。我们还发现了一个显着增加的分子伴侣，葡萄糖调节蛋白94（GRP 94）之间的BRG 1相关因子分离的FANCA突变细胞系，这是没有看到在正常对照细胞系或突变株补充野生型FANCA。尽管存在这种特异性差异，但FANCA似乎并不是体外染色质重塑所绝对需要的。最后，我们证明了转染的FANCA和BRG 1在细胞核中的共定位。FANCA对SWI/SNF复合物的生理作用仍有待澄清，但我们的工作表明，FANCA可能会招募SWI/SNF复合物靶向基因，从而使耦合核功能，如转录和DNA修复。
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 andbrm-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.