Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair

Koichi Sato, Masamichi Ishiai, Kazue Toda, Satoshi Furukoshi, Akihisa Osakabe, Hiroaki Tachiwana, Yoshimasa Takizawa, Wataru Kagawa, Hiroyuki Kitao, Naoshi Dohmae, Chikashi Obuse, Hiroshi Kimura, Minoru Takata, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    44 Citations (Scopus)

    Abstract

    Fanconi anaemia (FA) is a rare hereditary disorder characterized by genomic instability and cancer susceptibility. A key FA protein, FANCD2, is targeted to chromatin with its partner, FANCI, and plays a critical role in DNA crosslink repair. However, the molecular function of chromatin-bound FANCD2-FANCI is still poorly understood. In the present study, we found that FANCD2 possesses nucleosome-assembly activity in vitro. The mobility of histone H3 was reduced in FANCD2-knockdown cells following treatment with an interstrand DNA crosslinker, mitomycin C. Furthermore, cells harbouring FANCD2 mutations that were defective in nucleosome assembly displayed impaired survival upon cisplatin treatment. Although FANCI by itself lacked nucleosome-assembly activity, it significantly stimulated FANCD2-mediated nucleosome assembly. These observations suggest that FANCD2-FANCI may regulate chromatin dynamics during DNA repair.

    Original languageEnglish
    Pages (from-to)3524-3536
    Number of pages13
    JournalEMBO Journal
    Volume31
    Issue number17
    DOIs
    Publication statusPublished - 2012 Aug 29

    Keywords

    • DNA repair
    • FANCD2
    • FANCI
    • Fanconi anaemia
    • histone chaperone

    ASJC Scopus subject areas

    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)
    • Neuroscience(all)

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  • Cite this

    Sato, K., Ishiai, M., Toda, K., Furukoshi, S., Osakabe, A., Tachiwana, H., Takizawa, Y., Kagawa, W., Kitao, H., Dohmae, N., Obuse, C., Kimura, H., Takata, M., & Kurumizaka, H. (2012). Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair. EMBO Journal, 31(17), 3524-3536. https://doi.org/10.1038/emboj.2012.197