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Recombinant Antibody Expression> | … The monoclonal antibody against FAN1 was produced by GenScript (NJ, USA) by immunizing mice with recombinant His-tagged FAN1 (… * (Y128A/F129A/L155A/L159A) were purchased from GenScript and synthesized according to standard practice (N-terminal acetylation and … | Get A Quote |
FAN1, a DNA structure-specific nuclease, interacts with MLH1, but the repair pathways in which this complex acts are unknown. FAN1 processes DNA interstrand crosslinks (ICLs) and FAN1 variants are modifiers of the neurodegenerative Huntington's disease (HD), presumably by regulating HD-causing CAG repeat expansions. Here, we identify specific amino acid residues in two adjacent FAN1 motifs that are critical for MLH1 binding. Disruption of the FAN1-MLH1 interaction confers cellular hypersensitivity to ICL damage and defective repair of CAG/CTG slip-outs, intermediates of repeat expansion mutations. FAN1-S126 phosphorylation, which hinders FAN1-MLH1 association, is cell cycle-regulated by cyclin-dependent kinase ... More