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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 publication

DOI

10.1016/j.molcel.2008.12.003

Type

Journal article

Journal

Mol Cell

Publication Date

26/12/2008

Volume

32

Pages

767 - 777

Keywords

Amino Acid Sequence, Animals, Cell Line, Chickens, Conserved Sequence, Fanconi Anemia Complementation Group D2 Protein, Fanconi Anemia Complementation Group L Protein, Fanconi Anemia Complementation Group Proteins, Humans, Molecular Sequence Data, Protein Structure, Tertiary, Substrate Specificity, Ubiquitin-Conjugating Enzymes, Ubiquitination