| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Outline of Final Research Achievements |
DNA interstrand crosslink (ICL) prevents the progression of DNA replication and transcription by covalent crosslinking between complementary strands of double-stranded DNA. ICL repair is essential for suppression of chromosomal aberrations that contribute to cell death and tumorigenesis. Dual-incision around the crosslinked bases (ICL unhook) is a central step in the ICL repair. FAN1 is a structure-specific endonuclease that is considered to be involved in the ICL unhook. However, the mechanism how FAN1 recognizes the damaged bases and mediates the ICL unhook has remained elusive. In this study, our biochemical analyses with the purified FAN1 protein revealed the mechanism of the substrate-recognition and -incision by FAN1. In addition, we found that the FANCI-FANCD2 complex that recruits FAN1 to ICL sites functions to regulate the nuclease activity of FAN1.
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