Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions.
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.
Kusch
Thomas
T
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. tnk@stowers-institute.org
Florens
Laurence
L
Macdonald
W Hayes
WH
Swanson
Selene K
SK
Glaser
Robert L
RL
Yates
John R
JR
Abmayr
Susan M
SM
Washburn
Michael P
MP
Workman
Jerry L
JL
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
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