Originally published as Genetics Published Articles Ahead of Print on October 3, 2005.

Genetics, Vol. 172, 795-809, February 2006, Copyright © 2006
doi:10.1534/genetics.105.047589

The RSC Chromatin Remodeling Complex Bears an Essential Fungal-Specific Protein Module With Broad Functional Roles

* Howard Hughes Medical Institute and Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112 and {dagger} Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

1 Corresponding author: Howard Hughes Medical Institute and Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Room 4362, 2000 Circle of Hope, Salt Lake City, UT 84112.
E-mail: brad.cairns{at}hci.utah.edu

RSC is an essential and abundant ATP-dependent chromatin remodeling complex from Saccharomyces cerevisiae. Here we show that the RSC components Rsc7/Npl6 and Rsc14/Ldb7 interact physically and/or functionally with Rsc3, Rsc30, and Htl1 to form a module important for a broad range of RSC functions. A strain lacking Rsc7 fails to properly assemble RSC, which confers sensitivity to temperature and to agents that cause DNA damage, microtubule depolymerization, or cell wall stress (likely via transcriptional misregulation). Cells lacking Rsc14 display sensitivity to cell wall stress and are deficient in the assembly of Rsc3 and Rsc30. Interestingly, certain rsc7{Delta} and rsc14{Delta} phenotypes are suppressed by an increased dosage of Rsc3, an essential RSC member with roles in cell wall integrity and spindle checkpoint pathways. Thus, Rsc7 and Rsc14 have different roles in the module as well as sharing physical and functional connections to Rsc3. Using a genetic array of nonessential null mutations (SGA) we identified mutations that are sick/lethal in combination with the rsc7{Delta} mutation, which revealed connections to a surprisingly large number of chromatin remodeling complexes and cellular processes. Taken together, we define a protein module on the RSC complex with links to a broad spectrum of cellular functions.




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