title: Regulation of Rev1 by the Fanconi anemia core complex.
abstract: The 15 known Fanconi anemia proteins cooperate in a pathway that regulates DNA interstrand cross-link repair. Recent studies indicate that the Fanconi anemia pathway also controls Rev1-mediated translesion DNA synthesis (TLS). We identified Fanconi anemia-associated protein (FAAP20), an integral subunit of the multisubunit Fanconi anemia core complex. FAAP20 binds to FANCA subunit and is required for stability of the complex and monoubiquitination of FANCD2. FAAP20 contains a ubiquitin-binding zinc finger 4 domain and binds to the monoubiquitinated form of Rev1. FAAP20 binding stabilizes Rev1 nuclear foci and promotes interaction of the Fanconi anemia core with PCNA-Rev1 DNA damage bypass complexes. FAAP20 therefore provides a critical link between the Fanconi anemia pathway and TLS polymerase activity. We propose that the Fanconi anemia core complex regulates cross-link repair by channeling lesions to damage bypass pathways and preventing large DNA insertions and deletions.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Hyungjin
authors.initials: H
authors.lastname: Kim
authors.forename: Kailin
authors.initials: K
authors.lastname: Yang
authors.forename: Donniphat
authors.initials: D
authors.lastname: Dejsuphong
authors.forename: Alan D
authors.initials: AD
authors.lastname: D'Andrea
mesh_terms: D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D009687:Nuclear Proteins / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D000099270:Y-Family DNA Polymerases
chemical_list: D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; C570807:FAAP20 protein, human; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases