Biochemical analysis of a DNA crosslink repair protein, FAN1

2015 Fiscal Year Final Research Report

• Project/Area Number: 26830128
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Genome biology
• Research Institution: Waseda University
• Principal Investigator: SATO Koichi 早稲田大学, 理工学術院, 次席研究員(研究院助教) (60708585)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ゲノム維持修復 / Fanconi anemia / DNA crosslink / FAN1 / FANCD2 / FANCI / RAD51 / RPA

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.

Free Research Field

分子生物学、生化学