title: FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair.
abstract: 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.
authors.affiliation: Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Unno
authors.affiliation: Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan; Japan Society for the Promotion of Science (JSPS), Tokyo 102-0083, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Itaya
authors.affiliation: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Taoka
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.affiliation: Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Tomida
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology and Department of Biology, Graduate School of Science, Kobe University, Kobe, Hyogo 657-8501, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakai
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology and Department of Biology, Graduate School of Science, Kobe University, Kobe, Hyogo 657-8501, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
authors.affiliation: Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ishiai
authors.affiliation: Laboratory of Chromatin Regulatory Network, Department of Mutagenesis, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
authors.affiliation: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Isobe
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
authors.affiliation: Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan. Electronic address: mtakata@house.rbc.kyoto-u.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003432:Cross-Linking Reagents; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004706:Endodeoxyribonucleases; D005199:Fanconi Anemia / Q000235:genetics*; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D052236:Fanconi Anemia Complementation Group D2 Protein; D009687:Nuclear Proteins; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human