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    Mol Cell. 2008 Dec 26;32(6):767-77.

    Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI.

    Alpi AF, Pace PE, Babu MM, Patel KJ.

    Source

    Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.

    Abstract

    A key step in the Fanconi anemia (FA) tumor suppressor pathway is the site-specific monoubiquitination of the FANCD2 protein. Genetic studies indicate that this crucial modification requires eight known FA gene products and the E2-conjugating enzyme Ube2t. Here, we minimally reconstitute this monoubiquitination reaction with Ube2t and the FANCL protein, revealing that monoubiquitination is stimulated by a conserved RWD-like domain in FANCL. Furthermore, addition of the FANCI protein enhances monoubiquitination and also restricts it to the in vivo substrate lysine residue on FANCD2. This work therefore establishes a system that provides mechanistic insight into the functions of FANCL and FANCI in the catalysis of FANCD2 monoubiquitination.

    PMID:
    19111657
    [PubMed - indexed for MEDLINE]

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