FANCD2 Binds CtIP and Regulates DNA-End Resection during DNA Interstrand Crosslink Repair
Access this Article
小児の遺伝性疾患「ファンコニ貧血」病態の完全解明への一歩 ～キー分子FANCD2に会合するCtIPタンパク質の同定～. 京都大学プレスリリース. 2014-05-02.
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 MMCinduced 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.
- Cell Reports
Cell Reports (7), 1-9, 2014-05-22