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Originally published in Science Express on 4 November 2004
Science 17 December 2004:
Vol. 306. no. 5704, pp. 2084 - 2087
DOI: 10.1126/science.1103455
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Reports

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*

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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