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. 2004 Dec 17;306(5704):2084-7.
doi: 10.1126/science.1103455. Epub 2004 Nov 4.

Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions

Thomas Kusch  1 , Laurence Florens, W Hayes Macdonald, Selene K Swanson, Robert L Glaser, John R Yates 3rd, Susan M Abmayr, Michael P Washburn, Jerry L Workman
Affiliations

Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions

Thomas Kusch et al. Science. .

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.

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