title: The role of MOF in the ionizing radiation response is conserved in Drosophila melanogaster.
abstract: In Drosophila, males absent on the first (MOF) acetylates histone H4 at lysine 16 (H4K16ac). This acetylation mark is highly enriched on the male X chromosome and is required for dosage compensation in Drosophila but not utilized for such in mammals. Recently, we and others reported that mammalian MOF, through H4K16ac, has a critical role at multiple stages in the DNA damage response (DDR) and double-strand break repair pathways. The goal of this study was to test whether mof is similarly required for the response to ionizing radiation (IR) in Drosophila. We report that Drosophila mof mutations in males and females, as well as mof knockdown in SL-2 cells, reduce post-irradiation survival. MOF depletion in SL-2 cells also results in an elevated frequency of metaphases with chromosomal aberrations, suggesting that MOF is involved in DDR. Mutation in Drosophila mof also results in a defective mitotic checkpoint, enhanced apoptosis, and a defective p53 response post-irradiation. In addition, IR exposure enhanced H4K16ac levels in Drosophila as it also does in mammals. These results are the first to demonstrate a requirement for MOF in the whole animal IR response and suggest that the role of MOF in the response to IR is conserved between Drosophila and mammals.
authors.affiliation: Indian Institute of Chemical Technology, Hyderabad, AP 500007, India.
authors.forename: Manika P
authors.initials: MP
authors.lastname: Bhadra
authors.forename: Nobuo
authors.initials: N
authors.lastname: Horikoshi
authors.forename: Sreerangam N C V L
authors.initials: SN
authors.lastname: Pushpavallipvalli
authors.forename: Arpita
authors.initials: A
authors.lastname: Sarkar
authors.forename: Indira
authors.initials: I
authors.lastname: Bag
authors.forename: Anita
authors.initials: A
authors.lastname: Krishnan
authors.forename: John C
authors.initials: JC
authors.lastname: Lucchesi
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: Raj K
authors.initials: RK
authors.lastname: Pandita
authors.forename: Mayank
authors.initials: M
authors.lastname: Singh
authors.forename: Utpal
authors.initials: U
authors.lastname: Bhadra
authors.forename: Joel C
authors.initials: JC
authors.lastname: Eissenberg
authors.forename: Tej K
authors.initials: TK
authors.lastname: Pandita
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D017124:Conserved Sequence; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects*; D005260:Female; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008297:Male; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics*; D011839:Radiation, Ionizing
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D051548:Histone Acetyltransferases; C111063:mof protein, Drosophila
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