Mechanistic Insight into Site-Restricted Monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI

Arno F. Alpi, Paul E. Pace, M. Madan Babu, Ketan J. Patel (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    136 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)767-777
    Number of pages11
    JournalMolecular Cell
    Volume32
    Issue number6
    DOIs
    Publication statusPublished - 26 Dec 2008

    Keywords

    • ANEMIA CORE COMPLEX
    • DNA-DAMAGE RESPONSE
    • CROSS-LINK REPAIR
    • PATHWAY
    • PROTEIN
    • IDENTIFICATION
    • DOMAIN
    • UBIQUITINATION
    • CHROMATIN

    Cite this