FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair

Junya Unno, Akiko Itaya, Masato Taoka, Koichi Sato, Junya Tomida, Wataru Sakai, Kaoru Sugasawa, Masamichi Ishiai, Tsuyoshi Ikura, Toshiaki Isobe, Hitoshi Kurumizaka, Minoru Takata

    Research output: Contribution to journalArticle

    52 Citations (Scopus)

    Abstract

    The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and the suppression of carcinogenesis. A key FA protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms that are still poorly understood. Here, we report that CtIP protein directly interacts with FANCD2. A region spanning amino acids 166 to 273 of CtIP and monoubiquitination of FANCD2 are both essential for the FANCD2-CtIP interaction and mitomycin C (MMC)-induced CtIP foci. Remarkably, both FANCD2 and CtIP are critical for MMC-induced RPA2 hyperphosphorylation, an event that accompanies end resection of double-strand breaks. Collectively, our results reveal a role of monoubiquitinated FANCD2 in end resection that depends on its binding to CtIP during ICL repair.

    Original languageEnglish
    Pages (from-to)1039-1047
    Number of pages9
    JournalCell Reports
    Volume7
    Issue number4
    DOIs
    Publication statusPublished - 2014 May 22

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    Mitomycin
    Fanconi Anemia Complementation Group Proteins
    Repair
    Fanconi Anemia
    DNA
    Hematopoietic Stem Cells
    Stem cells
    DNA Repair
    Chromatin
    Carcinogenesis
    Maintenance
    Amino Acids
    Proteins

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

    Cite this

    Unno, J., Itaya, A., Taoka, M., Sato, K., Tomida, J., Sakai, W., ... Takata, M. (2014). FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair. Cell Reports, 7(4), 1039-1047. https://doi.org/10.1016/j.celrep.2014.04.005

    FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair. / Unno, Junya; Itaya, Akiko; Taoka, Masato; Sato, Koichi; Tomida, Junya; Sakai, Wataru; Sugasawa, Kaoru; Ishiai, Masamichi; Ikura, Tsuyoshi; Isobe, Toshiaki; Kurumizaka, Hitoshi; Takata, Minoru.

    In: Cell Reports, Vol. 7, No. 4, 22.05.2014, p. 1039-1047.

    Research output: Contribution to journalArticle

    Unno, J, Itaya, A, Taoka, M, Sato, K, Tomida, J, Sakai, W, Sugasawa, K, Ishiai, M, Ikura, T, Isobe, T, Kurumizaka, H & Takata, M 2014, 'FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair', Cell Reports, vol. 7, no. 4, pp. 1039-1047. https://doi.org/10.1016/j.celrep.2014.04.005
    Unno, Junya ; Itaya, Akiko ; Taoka, Masato ; Sato, Koichi ; Tomida, Junya ; Sakai, Wataru ; Sugasawa, Kaoru ; Ishiai, Masamichi ; Ikura, Tsuyoshi ; Isobe, Toshiaki ; Kurumizaka, Hitoshi ; Takata, Minoru. / FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair. In: Cell Reports. 2014 ; Vol. 7, No. 4. pp. 1039-1047.
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