A FancD2-Monoubiquitin Fusion Reveals Hidden Functions of Fanconi Anemia Core Complex in DNA Repair

作者: Nobuko Matsushita , Hiroyuki Kitao , Masamichi Ishiai , Naoki Nagashima , Seiki Hirano

DOI: 10.1016/J.MOLCEL.2005.08.018

关键词: FANCGBiologyFANCD2FAN1DNA repairMolecular biologyCell biologyChromatinFusion proteinFanconi anemia, complementation group CMonoubiquitination

摘要: In DNA damage responses, the Fanconi anemia (FA) protein, FancD2, is targeted to chromatin and forms nuclear foci following its monoubiquitination, a process likely catalyzed by FA core complex. Here, we show that chicken FancD2-ubiquitin fusion carrying Lys-Arg substitution removing natural monoubiquitination site (D2KR-Ub), could reverse cisplatin hypersensitivity localize in FANCD2-deficient DT40 cells. Importantly, targeting was dependent on three complex components as well hydrophobic surface of ubiquitin may direct protein-protein interactions. Furthermore, constitutively bound D2KR-histone H2B complement sensitivity FANCD2- but not FANCC-, FANCG-, or FANCL-deficient Thus these have an additional function repair, which independent FancD2. These results define functional consequences FancD2 reveal previously hidden functions for protein

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