DNA binding properties of the actin-related protein Arp8 and its role in DNA repair

Akihisa Osakabe, Yuichiro Takahashi, Hirokazu Murakami, Kenji Otawa, Hiroaki Tachiwana, Yukako Oma, Hitoshi Nishijima, Kei Ich Shibahara, Hitoshi Kurumizaka, Masahiko Harata

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    Actin and actin-related proteins (Arps), which are members of the actin family, are essential components of many of these remodeling complexes. Actin, Arp4, Arp5, and Arp8 are found to be evolutionarily conserved components of the INO80 chromatin remodeling complex, which is involved in transcriptional regulation, DNA replication, and DNA repair. A recent report showed that Arp8 forms a module in the INO80 complex and this module can directly capture a nucleosome. In the present study, we showed that recombinant human Arp8 binds to DNAs, and preferentially binds to single-stranded DNA. Analysis of the binding of adenine nucleotides to Arp8 mutants suggested that the ATP-binding pocket, located in the evolutionarily conserved actin fold, plays a regulatory role in the binding of Arp8 to DNA. To determine the cellular function of Arp8, we derived tetracycline-inducible Arp8 knockout cells from a cultured human cell line. Analysis of results obtained after treating these cells with aphidicolin and camptothecin revealed that Arp8 is involved in DNA repair. Together with the previous observation that Arp8, but not γ-H2AX, is indispensable for recruiting INO80 complex to DSB in human, results of our study suggest an individual role for Arp8 in DNA repair.

    Original languageEnglish
    Article numbere108354
    JournalPLoS One
    Volume9
    Issue number10
    DOIs
    Publication statusPublished - 2014 Oct 9

    Fingerprint

    binding properties
    DNA repair
    DNA Repair
    actin
    Actins
    Repair
    DNA
    Proteins
    proteins
    Aphidicolin
    Camptothecin
    single-stranded DNA
    nucleosomes
    Chromatin Assembly and Disassembly
    human cell lines
    Adenine Nucleotides
    Nucleosomes
    Single-Stranded DNA
    DNA replication
    Tetracycline

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Osakabe, A., Takahashi, Y., Murakami, H., Otawa, K., Tachiwana, H., Oma, Y., ... Harata, M. (2014). DNA binding properties of the actin-related protein Arp8 and its role in DNA repair. PLoS One, 9(10), [e108354]. https://doi.org/10.1371/journal.pone.0108354

    DNA binding properties of the actin-related protein Arp8 and its role in DNA repair. / Osakabe, Akihisa; Takahashi, Yuichiro; Murakami, Hirokazu; Otawa, Kenji; Tachiwana, Hiroaki; Oma, Yukako; Nishijima, Hitoshi; Shibahara, Kei Ich; Kurumizaka, Hitoshi; Harata, Masahiko.

    In: PLoS One, Vol. 9, No. 10, e108354, 09.10.2014.

    Research output: Contribution to journalArticle

    Osakabe, A, Takahashi, Y, Murakami, H, Otawa, K, Tachiwana, H, Oma, Y, Nishijima, H, Shibahara, KI, Kurumizaka, H & Harata, M 2014, 'DNA binding properties of the actin-related protein Arp8 and its role in DNA repair', PLoS One, vol. 9, no. 10, e108354. https://doi.org/10.1371/journal.pone.0108354
    Osakabe A, Takahashi Y, Murakami H, Otawa K, Tachiwana H, Oma Y et al. DNA binding properties of the actin-related protein Arp8 and its role in DNA repair. PLoS One. 2014 Oct 9;9(10). e108354. https://doi.org/10.1371/journal.pone.0108354
    Osakabe, Akihisa ; Takahashi, Yuichiro ; Murakami, Hirokazu ; Otawa, Kenji ; Tachiwana, Hiroaki ; Oma, Yukako ; Nishijima, Hitoshi ; Shibahara, Kei Ich ; Kurumizaka, Hitoshi ; Harata, Masahiko. / DNA binding properties of the actin-related protein Arp8 and its role in DNA repair. In: PLoS One. 2014 ; Vol. 9, No. 10.
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