FANCD2 Binds CtIP and Regulates DNA-End Resection during DNA Interstrand Crosslink Repair
Junya Unno,
Akiko Itaya,
Masato Taoka,
Koichi Sato,
Junya Tomida,
Wataru Sakai,
Kaoru Sugasawa,
Masamichi Ishiai,
Tsuyoshi Ikura,
Toshiaki Isobe,
Hitoshi Kurumizaka,
Minoru Takata
Affiliations
Junya Unno
Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan
Akiko Itaya
Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan
Masato Taoka
Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan
Koichi Sato
Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan
Junya Tomida
Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan
Wataru Sakai
Biosignal Research Center, Organization of Advanced Science and Technology and Department of Biology, Graduate School of Science, Kobe University, Kobe, Hyogo 657-8501, Japan
Kaoru Sugasawa
Biosignal Research Center, Organization of Advanced Science and Technology and Department of Biology, Graduate School of Science, Kobe University, Kobe, Hyogo 657-8501, Japan
Masamichi Ishiai
Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan
Tsuyoshi Ikura
Laboratory of Chromatin Regulatory Network, Department of Mutagenesis, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan
Toshiaki Isobe
Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan
Hitoshi Kurumizaka
Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan
Minoru Takata
Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan
The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and the suppression of carcinogenesis. A key FA protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms that are still poorly understood. Here, we report that CtIP protein directly interacts with FANCD2. A region spanning amino acids 166 to 273 of CtIP and monoubiquitination of FANCD2 are both essential for the FANCD2-CtIP interaction and mitomycin C (MMC)-induced CtIP foci. Remarkably, both FANCD2 and CtIP are critical for MMC-induced RPA2 hyperphosphorylation, an event that accompanies end resection of double-strand breaks. Collectively, our results reveal a role of monoubiquitinated FANCD2 in end resection that depends on its binding to CtIP during ICL repair.
