title: The human actin-related protein hArp5: nucleo-cytoplasmic shuttling and involvement in DNA repair.
abstract: Certain actin-related proteins (Arps) of budding yeast are localized in the nucleus, and have essential roles as stoichiometric components of histone acetyltransferase (HAT) and chromatin remodeling complexes. On the other hand, identification of vertebrate nuclear Arps and their functional analyses are just beginning. We show that human Arp5 (hArp5) proteins are localized in the nucleus, and that arp5Delta yeast cells are partially complemented by hArp5. Thus, hArp5 is a novel member of the nuclear Arps of vertebrates, which possess evolutionarily conserved functions from yeast to humans. We show here that hArp5 shuttles between the nucleus and the cytoplasm. Furthermore, after the induction of DNA double strand breaks (DSB), cell growth and the accumulation of phosphorylated histone H2AX (gamma-H2AX) are impaired by hArp5 depletion. Association of hArp5 with the hIno80 chromatin remodeling enzyme and decrease of chromatin-bound hIno80 by hArp5-depletion indicate that hArp5 may have a role in the recruitment of the hINO80 complex to chromatin. Overexpression of hArp5 and hIno80 enhanced gamma-H2AX accumulation. These observations suggest that hArp5 is involved in the process of DSB repair through the regulation of the chromatin remodelling machinery.
authors.affiliation: Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kitayama
authors.forename: Mariko
authors.initials: M
authors.lastname: Kamo
authors.forename: Yukako
authors.initials: Y
authors.lastname: Oma
authors.forename: Ryo
authors.initials: R
authors.lastname: Matsuda
authors.forename: Takafumi
authors.initials: T
authors.lastname: Uchida
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tashiro
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohyama
authors.forename: Barbara
authors.initials: B
authors.lastname: Winsor
authors.forename: Masahiko
authors.initials: M
authors.lastname: Harata
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000502:physiology*; D064007:Ataxia Telangiectasia Mutated Proteins; D001761:Bleomycin / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000037:antagonists & inhibitors; D019913:Nuclear Localization Signals / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014170:Transformation, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D000074183:ATPases Associated with Diverse Cellular Activities; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D064007:Ataxia Telangiectasia Mutated Proteins; D001761:Bleomycin; D018797:Cell Cycle Proteins; D002843:Chromatin; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; D006657:Histones; D028884:Karyopherins; D019913:Nuclear Localization Signals; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D000097606:Exportin 1 Protein; C477601:ANGPTL6 protein, human; C468783:H2AX protein, human; C576324:ATM protein, human; C524421:INO80 protein, human; C038753:leptomycin B