Flom Gary, Weekes Jared, Johnson Jill L
Department of Microbiology, Molecular Biology and Biochemistry, Center for Reproductive Biology, University of Idaho, Moscow, ID 83844-3052, USA.
Curr Genet. 2005 Jun;47(6):368-80. doi: 10.1007/s00294-005-0580-6. Epub 2005 May 4.
Hsp90 is an essential molecular chaperone that is critical for the activity of diverse cellular proteins. Hsp90 functions with a number of co-chaperone proteins, including Sti1/Hop. We conducted a genetic screen in Saccharomyces cerevisiae to isolate mutations that exhibit enhanced growth defects in the absence of STI1. We obtained mutations in genes encoding components of the Hsp90 chaperone machine, HSC82, CPR7 and YDJ1, and two essential genes, SSL2 and UTP21, not previously linked to Hsp90. Ssl2, the yeast homologue of XPB, is an ATP-dependent DNA helicase that is a component of the TFIIH multiprotein complex and has dual functions in transcription and DNA repair. In order to determine whether Ssl2 function is dependent on Hsp90, we further examined the interaction between Ssl2 and Hsp90. Multiple mutant alleles of SSL2 exhibited a pronounced growth defect when co-expressed with a mutant allele of Hsp90. In addition, isolation of Ssl2 protein resulted in the co-purification of Hsp90 and Sti1, suggesting that Ssl2 and Hsp90 are in the same protein complexes in vivo. These results suggest a novel role for Hsp90 in the essential cellular functions of transcription and DNA repair.
热休克蛋白90（Hsp90）是一种必需的分子伴侣，对多种细胞蛋白的活性至关重要。Hsp90与许多共伴侣蛋白一起发挥作用，包括Sti1/Hop。我们在酿酒酵母中进行了遗传筛选，以分离出在缺乏STI1时表现出增强生长缺陷的突变。我们在编码Hsp90伴侣机器组分的基因HSC82、CPR7和YDJ1以及两个以前未与Hsp90相关联的必需基因SSL2和UTP21中获得了突变。Ssl2是XPB的酵母同源物，是一种ATP依赖性DNA解旋酶，是TFIIH多蛋白复合物的一个组分，在转录和DNA修复中具有双重功能。为了确定Ssl2的功能是否依赖于Hsp90，我们进一步研究了Ssl2与Hsp90之间的相互作用。当与Hsp90的突变等位基因共表达时，SSL2的多个突变等位基因表现出明显的生长缺陷。此外，Ssl2蛋白的分离导致Hsp90和Sti1的共纯化，表明Ssl2和Hsp90在体内处于相同的蛋白复合物中。这些结果表明Hsp90在转录和DNA修复的基本细胞功能中具有新的作用。
