Jeannine Gerhardt, Angela D. Bhalla, Jill Sergesketter Butler, James W. Puckett, Peter B. Dervan, Zev Rosenwaks, Marek Napierala, Cell Reports, Available online 14 July 2016, ISSN 2211-1247, doi:10.1016/j.celrep.2016.06.075.
Using single-molecule analysis of replicated DNA, we detected that expanded GAA repeats present a substantial obstacle for the replication machinery at the FXN locus in FRDA cells. Furthermore, aberrant origin activation and lack of a proper stress response to rescue the stalled forks in FRDA cells cause an increase in 3′-5′ progressing forks, which could enhance repeat expansion and hinder FXN transcription by head-on collision with RNA polymerases.
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