CTG repeats show bimodal amplification in E-coli

Trinucleotide repeats in human genetic disorders showing anticipation follow two inheritance patterns as a function of length. Inheritance of 35-50 repeats show incremental changes, white tracts greater than 80 repeats show large saltatory expansions. We describe a bacterial system that recapitulates this striking bimodal pattern of CTG amplification. Incremental expansions predominate in CTG tracts greater than or equal to Okazaki fragment size, while saltatory expansions increase in repeat tracts greater than or equal to Okazaki fragment size. CTG amplification requires loss of SbcC, a protein that modulates cleavage of single-stranded DNA and degradation of duplex DNA from double-strand breaks. These results suggest that noncanonical single strand-containing secondary structures in Okazaki fragments and/or double-strand breaks in repeat tracts are intermediates in CTG amplification.