FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end

Koichi Sato, Mayo Shimomuki, Yoko Katsuki, Daisuke Takahashi, Wataru Kobayashi, Masamichi Ishiai, Hiroyuki Miyoshi, Minoru Takata, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-Associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork.

    Original languageEnglish
    Pages (from-to)10758-10771
    Number of pages14
    JournalNucleic Acids Research
    Volume44
    Issue number22
    DOIs
    Publication statusPublished - 2016 Dec 1

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    DNA
    Genomic Instability

    ASJC Scopus subject areas

    • Genetics

    Cite this

    Sato, K., Shimomuki, M., Katsuki, Y., Takahashi, D., Kobayashi, W., Ishiai, M., ... Kurumizaka, H. (2016). FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end. Nucleic Acids Research, 44(22), 10758-10771. https://doi.org/10.1093/nar/gkw876

    FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end. / Sato, Koichi; Shimomuki, Mayo; Katsuki, Yoko; Takahashi, Daisuke; Kobayashi, Wataru; Ishiai, Masamichi; Miyoshi, Hiroyuki; Takata, Minoru; Kurumizaka, Hitoshi.

    In: Nucleic Acids Research, Vol. 44, No. 22, 01.12.2016, p. 10758-10771.

    Research output: Contribution to journalArticle

    Sato, K, Shimomuki, M, Katsuki, Y, Takahashi, D, Kobayashi, W, Ishiai, M, Miyoshi, H, Takata, M & Kurumizaka, H 2016, 'FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end', Nucleic Acids Research, vol. 44, no. 22, pp. 10758-10771. https://doi.org/10.1093/nar/gkw876
    Sato, Koichi ; Shimomuki, Mayo ; Katsuki, Yoko ; Takahashi, Daisuke ; Kobayashi, Wataru ; Ishiai, Masamichi ; Miyoshi, Hiroyuki ; Takata, Minoru ; Kurumizaka, Hitoshi. / FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end. In: Nucleic Acids Research. 2016 ; Vol. 44, No. 22. pp. 10758-10771.
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    abstract = "The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-Associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork.",
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    AU - Ishiai, Masamichi

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