title: Removal of H2A.Z by INO80 promotes homologous recombination.
abstract: The mammalian INO80 remodelling complex facilitates homologous recombination (HR), but the mechanism by which it does this is unclear. Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. H2A.Z is actively incorporated at sites of damage in mammalian cells, raising the possibility that H2A.Z may need to be subsequently removed for resolution of repair. Here, we show that H2A.Z in human cells is indeed rapidly removed from chromatin flanking DNA damage by INO80. We also report that the histone chaperone ANP32E, which is implicated in removing H2AZ from chromatin, similarly promotes HR and appears to work on the same pathway as INO80 in these assays. Importantly, we demonstrate that the HR defect in cells depleted of INO80 or ANP32E can be rescued by H2A.Z co-depletion, suggesting that H2A.Z removal from chromatin is the primary function of INO80 and ANP32E in promoting homologous recombination.
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, UK.
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Alatwi
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, UK j.a.downs@sussex.ac.uk.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Downs
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D059765:Homologous Recombination; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering
chemical_list: C490336:ANP32E protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C077020:histone H2A.F-Z; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C524421:INO80 protein, human
keywords: ANP32E; H2A.Z; INO80; chromatin; homologous recombination