Regulation of Rev1 by the Fanconi Anemia Core Complex

The fifteen known Fanconi Anemia (FA) proteins cooperate in a pathway which regulates DNA interstrand crosslink repair. Recent studies indicate that the FA pathway also controls Rev1-mediated translesion DNA synthesis (TLS). Here we identify a novel protein FAAP20, which is an integral subunit of the multisubunit FA core complex. FAAP20 binds to FANCA subunit and is required for complex stability and monoubiquitination of FANCD2. FAAP20 contains a UBZ4 (Ubiquitin Binding Zinc finger 4) domain and binds to the monoubiquitinated form of Rev1. FAAP20 binding stabilizes Rev1 nuclear foci and promotes the interaction of the FA core with PCNA/Rev1 DNA damage bypass complexes. FAAP20 therefore provides a critical link between the FA pathway and TLS polymerase activity. We propose that the FA core complex regulates crosslink repair, by channeling lesions to damage bypass pathways and preventing large DNA insertions and deletions.