Fig. 1: Generating lethal DNA damage in a genome amplification dependent manner. | Nature Communications

Fig. 1: Generating lethal DNA damage in a genome amplification dependent manner.

From: Selective targeting of genome amplifications and repeat elements by CRISPR-Cas9 nickases to promote cancer cell death

Fig. 1

A Top pathway: Transient single-strand breaks (SSBs) are largely innocuous and quickly repaired in non-dividing cells. Bottom pathway: Persistent SSBs at high copy number loci within the genome in proliferating cells can induce cellular toxicity through their conversion into single-ended double-strand breaks (seDSBs) during DNA replication. Created in BioRender. Wolfe, S. (2025) https://BioRender.com/ttl9vxt. B Average MYCN genome copy number across various neuroblastoma cell lines obtained by qPCR (n = ≥ 3 biological replicates). For each box plot the horizontal line represents the median, the top and bottom of the box represent the upper and lower quartiles, respectively, and the top and bottom whiskers represent the maximum and minimum values, respectively. C A schematic of piggyBac-integrated sgRNA expression cassettes used to generate stable sgRNA-expressing cell lines. D A schematic of in vitro transcribed Cas9 nickase – mRNA construct variants. Created in BioRender. Wolfe, S. (2025) https://BioRender.com/tgt62po. Source data are provided as a Source Data file.

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