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

    研究成果: Article査読

    56 被引用数 (Scopus)

    抄録

    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.

    本文言語English
    ページ(範囲)1039-1047
    ページ数9
    ジャーナルCell Reports
    7
    4
    DOI
    出版ステータスPublished - 2014 5 22

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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