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Science 306 (5704): 2084-2087

Copyright © 2004 by the American Association for the Advancement of Science

Acetylation by Tip60 Is Required for Selective Histone Variant Exchange at DNA Lesions

Thomas Kusch,1* Laurence Florens,1 W. Hayes MacDonald,2 Selene K. Swanson,1 Robert L. Glaser,3 John R. Yates, III,2 Susan M. Abmayr,1 Michael P Washburn,1 Jerry L. Workman1*

Abstract: Phosphorylation of the human histone variant H2A.X and H2Av, its homolog in Drosophila melanogaster, occurs rapidly at sites of DNA double-strand breaks. Little is known about the function of this phosphorylation or its removal during DNA repair. Here, we demonstrate that the Drosophila Tip60 (dTip60) chromatin-remodeling complex acetylates nucleosomal phospho-H2Av and exchanges it with an unmodified H2Av. Both the histone acetyltransferase dTip60 as well as the adenosine triphosphatase Domino/p400 catalyze the exchange of phospho-H2Av. Thus, these data reveal a previously unknown mechanism for selective histone exchange that uses the concerted action of two distinct chromatin-remodeling enzymes within the same multiprotein complex.

1 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
2 Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
3 Wadsworth Center, New York State Department of Health, Post Office Box 22002, Albany, NY 12201, USA.

* To whom correspondence should be addressed. E-mail: tnk{at}stowers-institute.org (T.K.); jlw{at}stowers-institute.org (J.L.W.)

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A. V. Samuelson, M. Narita, H.-M. Chan, J. Jin, E. de Stanchina, M. E. McCurrach, M. Narita, M. Fuchs, D. M. Livingston, and S. W. Lowe (2005)
J. Biol. Chem. 280, 21915-21923
   Abstract »    Full Text »    PDF »
Tails of histones in DNA double-strand break repair.
E. Bilsland and J. A. Downs (2005)
Mutagenesis 20, 153-163
   Abstract »    Full Text »    PDF »
MRG15 Regulates Embryonic Development and Cell Proliferation.
K. Tominaga, B. Kirtane, J. G. Jackson, Y. Ikeno, T. Ikeda, C. Hawks, J. R. Smith, M. M. Matzuk, and O. M. Pereira-Smith (2005)
Mol. Cell. Biol. 25, 2924-2937
   Abstract »    Full Text »    PDF »

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