A FancD2-monoubiquitin fusion reveals hidden functions of Fanconi anemia core complex in DNA repair

Nobuko Matsushita, Hiroyuki Kitao, Masamichi Ishiai, Naoki Nagashima, Seiki Hirano, Katsuya Okawa, Tomohiko Ohta, David S. Yu, Peter J. McHugh, Ian D. Hickson, Ashok R. Venkitaraman, Hitoshi Kurumizaka, Minoru Takata

    Research output: Contribution to journalArticle

    108 Citations (Scopus)

    Abstract

    In DNA damage responses, the Fanconi anemia (FA) protein, FancD2, is targeted to chromatin and forms nuclear foci following its monoubiquitination, a process likely catalyzed by the FA core complex. Here, we show that a chicken FancD2-ubiquitin fusion protein, carrying a Lys-Arg substitution removing the natural monoubiquitination site (D2KR-Ub), could reverse cisplatin hypersensitivity and localize to chromatin in FANCD2-deficient DT40 cells. Importantly, the chromatin targeting was dependent on three core complex components as well as the hydrophobic surface of ubiquitin that may direct protein-protein interactions. Furthermore, a constitutively chromatin bound fusion of D2KR-histone H2B could complement cisplatin sensitivity in FANCD2- but not FANCC-, FANCG-, or FANCL-deficient cells. Thus these core complex components have an additional function in the DNA repair, which is independent of the monoubiquitination and chromatin targeting of FancD2. These results define functional consequences of FancD2 monoubiquitination and reveal previously hidden functions for the FA protein core complex.

    Original languageEnglish
    Pages (from-to)841-847
    Number of pages7
    JournalMolecular Cell
    Volume19
    Issue number6
    DOIs
    Publication statusPublished - 2005 Sep 16

    Fingerprint

    Fanconi Anemia
    DNA Repair
    Chromatin
    Fanconi Anemia Complementation Group Proteins
    Ubiquitin
    Cisplatin
    Proteins
    Histones
    DNA Damage
    Chickens
    Hypersensitivity

    ASJC Scopus subject areas

    • Molecular Biology

    Cite this

    Matsushita, N., Kitao, H., Ishiai, M., Nagashima, N., Hirano, S., Okawa, K., ... Takata, M. (2005). A FancD2-monoubiquitin fusion reveals hidden functions of Fanconi anemia core complex in DNA repair. Molecular Cell, 19(6), 841-847. https://doi.org/10.1016/j.molcel.2005.08.018

    A FancD2-monoubiquitin fusion reveals hidden functions of Fanconi anemia core complex in DNA repair. / Matsushita, Nobuko; Kitao, Hiroyuki; Ishiai, Masamichi; Nagashima, Naoki; Hirano, Seiki; Okawa, Katsuya; Ohta, Tomohiko; Yu, David S.; McHugh, Peter J.; Hickson, Ian D.; Venkitaraman, Ashok R.; Kurumizaka, Hitoshi; Takata, Minoru.

    In: Molecular Cell, Vol. 19, No. 6, 16.09.2005, p. 841-847.

    Research output: Contribution to journalArticle

    Matsushita, N, Kitao, H, Ishiai, M, Nagashima, N, Hirano, S, Okawa, K, Ohta, T, Yu, DS, McHugh, PJ, Hickson, ID, Venkitaraman, AR, Kurumizaka, H & Takata, M 2005, 'A FancD2-monoubiquitin fusion reveals hidden functions of Fanconi anemia core complex in DNA repair', Molecular Cell, vol. 19, no. 6, pp. 841-847. https://doi.org/10.1016/j.molcel.2005.08.018
    Matsushita, Nobuko ; Kitao, Hiroyuki ; Ishiai, Masamichi ; Nagashima, Naoki ; Hirano, Seiki ; Okawa, Katsuya ; Ohta, Tomohiko ; Yu, David S. ; McHugh, Peter J. ; Hickson, Ian D. ; Venkitaraman, Ashok R. ; Kurumizaka, Hitoshi ; Takata, Minoru. / A FancD2-monoubiquitin fusion reveals hidden functions of Fanconi anemia core complex in DNA repair. In: Molecular Cell. 2005 ; Vol. 19, No. 6. pp. 841-847.
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