Abstract
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, while 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 < Okazaki fragment size, while saltatory expansions increase in repeat tracts ≥ 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.
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