Defective FANCI binding by a fanconi anemia-related FANCD2 mutant

Koichi Sato, Masamichi Ishiai, Minoru Takata, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    FANCD2 is a product of one of the genes associated with Fanconi anemia (FA), a rare recessive disease characterized by bone marrow failure, skeletal malformations, developmental defects, and cancer predisposition. FANCD2 forms a complex with FANCI (ID complex) and is monoubiquitinated, which facilitates the downstream interstrand crosslink (ICL) repair steps, such as ICL unhooking and nucleolytic end resection. In the present study, we focused on the chicken FANCD2 (cFANCD2) mutant harboring the Leu234 to Arg (L234R) substitution. cFANCD2 L234R corresponds to the human FANCD2 L231R mutation identified in an FA patient. We found that cFANCD2 L234R did not complement the defective ICL repair in FANCD22/2 DT40 cells. Purified cFANCD2 L234R did not bind to chicken FANCI, and its monoubiquitination was significantly deficient, probably due to the abnormal ID complex formation. In addition, the histone chaperone activity of cFANCD2 L234R was also defective. These findings may explain some aspects of Fanconi anemia pathogenesis by a FANCD2 missense mutation.

    Original languageEnglish
    Article numbere114752
    JournalPLoS One
    Volume9
    Issue number12
    DOIs
    Publication statusPublished - 2014 Dec 9

    Fingerprint

    Fanconi Anemia
    Chickens
    Repair
    Histone Chaperones
    chickens
    mutants
    Bone
    Substitution reactions
    Genes
    Defects
    missense mutation
    resection
    Missense Mutation
    Rare Diseases
    histones
    bone marrow
    Fanconi anemia
    complement
    pathogenesis
    Bone Marrow

    ASJC Scopus subject areas

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

    Cite this

    Sato, K., Ishiai, M., Takata, M., & Kurumizaka, H. (2014). Defective FANCI binding by a fanconi anemia-related FANCD2 mutant. PLoS One, 9(12), [e114752]. https://doi.org/10.1371/journal.pone.0114752

    Defective FANCI binding by a fanconi anemia-related FANCD2 mutant. / Sato, Koichi; Ishiai, Masamichi; Takata, Minoru; Kurumizaka, Hitoshi.

    In: PLoS One, Vol. 9, No. 12, e114752, 09.12.2014.

    Research output: Contribution to journalArticle

    Sato, K, Ishiai, M, Takata, M & Kurumizaka, H 2014, 'Defective FANCI binding by a fanconi anemia-related FANCD2 mutant', PLoS One, vol. 9, no. 12, e114752. https://doi.org/10.1371/journal.pone.0114752
    Sato, Koichi ; Ishiai, Masamichi ; Takata, Minoru ; Kurumizaka, Hitoshi. / Defective FANCI binding by a fanconi anemia-related FANCD2 mutant. In: PLoS One. 2014 ; Vol. 9, No. 12.
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