A chromatin remodelling complex involved in transcription and DNA processing

Abstract

The packaging of the eukaryotic genome in chromatin presents barriers that restrict the access of enzymes that process DNA^1,2. To overcome these barriers, cells possess a number of multi-protein, ATP-dependent chromatin remodelling complexes, each containing an ATPase subunit from the SNF2/SWI2 superfamily^3,4. Chromatin remodelling complexes function by increasing nucleosome mobility and are clearly implicated in transcription^5,6,7. Here we have analysed SNF2/SWI2- and ISWI-related proteins to identify remodelling complexes that potentially assist other DNA transactions. We purified a complex from Saccharomyces cerevisiae that contains the Ino80 ATPase⁸. The INO80 complex contains about 12 polypeptides including two proteins related to the bacterial RuvB DNA helicase^9,10,11, which catalyses branch migration of Holliday junctions. The purified complex remodels chromatin, facilitates transcription in vitro and displays 3′ to 5′ DNA helicase activity. Mutants of ino80 show hypersensitivity to agents that cause DNA damage, in addition to defects in transcription⁸. These results indicate that chromatin remodelling driven by the Ino80 ATPase may be connected to transcription as well as DNA damage repair.