title: Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions.
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.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. tnk@stowers-institute.org
authors.forename: Thomas
authors.initials: T
authors.lastname: Kusch
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: W Hayes
authors.initials: WH
authors.lastname: Macdonald
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.forename: Robert L
authors.initials: RL
authors.lastname: Glaser
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abmayr
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D019281:Dimerization; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D006657:Histones; D046912:Multiprotein Complexes; D009707:Nucleosomes; D011994:Recombinant Proteins; D014157:Transcription Factors; D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D000251:Adenosine Triphosphatases