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Rad4–Rad23 interaction with SWI/SNF links ATP-dependent chromatin remodeling with nucleotide excision repair

Abstract

Chromatin rearrangement occurs during nucleotide excision repair (NER). Here we show that Snf6 and Snf5, two subunits of the SWI/SNF chromatin-remodeling complex in Saccharomyces cerevisiae, copurify with the NER damage-recognition heterodimer Rad4–Rad23. This interaction between SWI/SNF and Rad4–Rad23 is stimulated by UV irradiation. We demonstrate that NER in the transcriptionally silent, nucleosome-loaded HML locus is reduced in yeast cells lacking functional SWI/SNF. In addition, using a restriction enzyme accessibility assay, we observed UV-induced nucleosome rearrangement at the silent HML locus. Notably, this rearrangement is markedly attenuated when SWI/SNF is inactivated. These results indicate that the SWI/SNF chromatin-remodeling complex is recruited to DNA lesions by damage-recognition proteins to increase DNA accessibility for NER in chromatin.

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Figure 1: Interaction between Rad23 and SWI/SNF.
Figure 2: Interaction between Rad4 and SWI/SNF.
Figure 3: Evidence for direct Snf6-Rad4 interaction.
Figure 4: Inactivation of SWI/SNF affects the rate of GGR at the silent HML locus in yeast cells.
Figure 5: Lack of evidence for Snf6-Rad16 interaction.
Figure 6: Model depicting involvement of the chromatin-remodeling complex SWI/SNF during NER in chromatin.

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Acknowledgements

We are grateful to E. O'Shea for supplying yeast strains at an early stage of this study. This study was made possible by US National Institutes of Health grants ES02614 and ES04106 from the National Institute of Environmental Health Sciences (to M.J.S.) and grant IRG-77-003-26 from the American Cancer Society (to F.G.).

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F.G. and M.J.S designed the experiments. F.G. and D.F. did the experiments. F.G., D.F. and M.J.S interpreted the results. F.G. prepared the manuscript and M.J.S., D.F. and F.G. revised the manuscript.

Corresponding authors

Correspondence to Feng Gong or Michael J Smerdon.

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The authors declare no competing financial interests.

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Gong, F., Fahy, D. & Smerdon, M. Rad4–Rad23 interaction with SWI/SNF links ATP-dependent chromatin remodeling with nucleotide excision repair. Nat Struct Mol Biol 13, 902–907 (2006). https://doi.org/10.1038/nsmb1152

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