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Updated: Jul 31, 2026

CD Spectroscopy to Study DNA-Protein Interactions
Published on: February 10, 2022
Inhibition of FEN-1 processing by DNA secondary structure at trinucleotide repeats
C Spiro1, R Pelletier, M L Rolfsmeier
1Department of Pharmacology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Abstract:
The mechanism by which trinucleotide expansion occurs in human genes is not understood. However, it has been hypothesized that DNA secondary structure may actively participate by preventing FEN-1 cleavage of displaced Okazaki fragments. We show here that secondary structure can, indeed, play a role in expansion by a FEN-1-dependent mechanism. Secondary structure inhibits flap processing at CAG, CGG, or CTG repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by FEN-1. Thus, secondary structure can defeat the protective function of FEN-1, leading to site-specific expansions. However, when FEN-1 is absent from the cell, alternative pathways to simple inhibition of flap processing contribute to expansion.
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