Cell Rep 2021 12;37(10):110078
Program of Genetics & Genome Biology, The Hospital for Sick Children, PGCRL, Toronto, Canada, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Program of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:
Ongoing inchworm-like CAG and CGG repeat expansions in brains, arising by aberrant processing of slipped DNAs, may drive Huntington's disease, fragile X syndrome, and autism. FAN1 nuclease modifies hyper-expansion rates by unknown means. We show that FAN1, through iterative cycles, binds, dimerizes, and cleaves slipped DNAs, yielding striking exo-nuclease pauses along slip-outs: 5'-C↓A↓GC↓A↓G-3' and 5'-C↓T↓G↓C↓T↓G-3'. Read More