The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL*

Abstract Background: The E3 ligase FANCL monoubiquitinates FANCD2 in a critical step in the repair of DNA interstrand crosslinks. Results: FANCL binds ubiquitin non-covalently via its N-terminal E2-like fold. Conclusion: Monoubiquitination of FANCD2 is regulated via a non-covalent interaction between FANCL and ubiquitin. Significance: This interaction represents an additional layer of regulation of the Fanconi Anemia pathway, and a targetable interface. Article type: Research Article Keywords: DNA repair, E3 ubiquitin ligase, isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR), ubiquitin,