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, 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 > or = 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.
Sarkar
P S
PS
Institute for Genetic Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
Chang
H C
HC
Boudi
F B
FB
Reddy
S
S
D001426:Bacterial Proteins / Q000096:biosynthesis / Q000502:physiology; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D004269:DNA, Bacterial / Q000235:genetics* / Q000502:physiology; D003851:Deoxyribonucleases / Q000096:biosynthesis / Q000502:physiology; D004706:Endodeoxyribonucleases / Q000096:biosynthesis / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins; D019143:Evolution, Molecular; D005090:Exodeoxyribonucleases / Q000096:biosynthesis / Q000502:physiology; D005784:Gene Amplification; D018911:Trinucleotide Repeats
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C022262:Okazaki fragments; C061563:SbcC protein, Bacteria; C489229:SbcC protein, E coli; D004247:DNA; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases