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Molecular and Cellular Biology, September 2003, p. 6086-6102, Vol. 23, No. 17
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.17.6086-6102.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Yaf9, a Novel NuA4 Histone Acetyltransferase Subunit, Is Required for the Cellular Response to Spindle Stress in Yeast

Ivan Le Masson,1 David Y. Yu,2 Kurt Jensen,2 Anne Chevalier,1 Régis Courbeyrette,1 Yves Boulard,1 M. Mitchell Smith,2 and Carl Mann1*

Service de Biochimie et de Génétique Moléculaire, CEA/Saclay, 91191 Gif-sur-Yvette, France,1 Department of Microbiology, University of Virginia, Charlottesville, Virginia 229082

Received 11 February 2003/ Returned for modification 10 April 2003/ Accepted 2 June 2003

Yaf9 is one of three proteins in budding yeast containing a YEATS domain. We show that Yaf9 is part of a large complex and that it coprecipitates with three known subunits of the NuA4 histone acetyltransferase. Although Esa1, the catalytic subunit of NuA4, is essential for viability, we found that yaf9{Delta} mutants are viable but hypersensitive to microtubule depolymerizing agents and synthetically lethal with two different mutants of the mitotic apparatus. Microtubules depolymerized more readily in the yaf9{Delta} mutant compared to the wild type in the presence of nocodazole, and recovery of microtubule polymerization and cell division from limiting concentrations of nocodazole was inhibited. Two other NuA4 mutants (esa1-1851 and yng2{Delta}) and nonacetylatable histone H4 mutants were also sensitive to benomyl. Furthermore, wild-type budding yeast were more resistant to benomyl when grown in the presence of trichostatin A, a histone deacetylase inhibitor. These results strongly suggest that acetylation of histone H4 by NuA4 is required for the cellular resistance to spindle stress.

* Corresponding author. Mailing address: SBGM-BÂt. 144, CEA/Saclay, F-91191 Gif-sur-Yvette Cedex, France. Phone: (33) 1-69-08-34-32. Fax: (33) 1-69-08-47-12. E-mail: cmann{at}cea.fr.

Molecular and Cellular Biology, September 2003, p. 6086-6102, Vol. 23, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.17.6086-6102.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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