Defective FANCI binding by a fanconi anemia-related FANCD2 mutant

Koichi Sato, Masamichi Ishiai, Minoru Takata, Hitoshi Kurumizaka*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    5 Citations (Scopus)


    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
    Issue number12
    Publication statusPublished - 2014 Dec 9

    ASJC Scopus subject areas

    • General Agricultural and Biological Sciences
    • General Biochemistry,Genetics and Molecular Biology
    • General Medicine


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