CTG repeats show bimodal amplification in E. coli

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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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Sarkar, P. S., Chang, H. C., Boudi, F. B., & Reddy, S. (1998). CTG repeats show bimodal amplification in E. coli. Cell, 95(4), 531–540. https://doi.org/10.1016/S0092-8674(00)81620-7

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