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A chromatin remodelling complex involved in transcription and DNA processing

Nature volume 406, pages 541–544 (2000)Cite this article

Abstract

The packaging of the eukaryotic genome in chromatin presents barriers that restrict the access of enzymes that process DNA1,2. 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 superfamily3,4. Chromatin remodelling complexes function by increasing nucleosome mobility and are clearly implicated in transcription5,6,7. 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 helicase9,10,11, 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.

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Figure 1: Purification and characterization of the INO80 complex.
Figure 2: Rvb1 and Rvb2 are subunits of the INO80 complex.
Figure 3: INO80 complex has 3′ to 5′ specific helicase activity.
Figure 4: INO80 complex remodels and promotes transcription from a chromatin template.
Figure 5: Analysis of ino80 mutant phenotypes.

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Acknowledgements

We thank T. Tsukiyama and the CSHL yeast genetics course 1998 for expert training, and members of our lab for help and discussion. We also thank Y. Nakatani, J. Pradel and J. Cote for sharing results; W. S. Lane for peptide sequencing; F. Winston and D. E. Gottschling for yeast strains; and M. Lichten and G. Storz for helpful comments on the manuscript. X.S. was supported by the American Cancer Society, and A.H. was supported by the Human Frontiers of Science Program. This work was supported by the Intramural Research Program of the National Cancer Institute.

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Authors and Affiliations

  1. Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda , 20892-4255, Maryland, USA

    Xuetong Shen, Ali Hamiche & Carl Wu

  2. Kyoto University Graduate School of Biostudies, Sakyo-ku, 606-8502, Kyoto, Japan

    Gaku Mizuguchi

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Shen, X., Mizuguchi, G., Hamiche, A. et al. A chromatin remodelling complex involved in transcription and DNA processing. Nature 406, 541–544 (2000). https://doi.org/10.1038/35020123

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