The specificity and structure of DNA crosslinking by the gut bacterial genotoxin colibactin

We report here LC-MS data, used in conjunction with NMR analysis, to elucidate the specificity and structure of interstrand crosslinks (ICL) of DNA resulting from the genotoxin colibactin. The measured masses of 14- and 25-mer double strand DNA oligomers exposed to colibactin provided for the determination of the chemical structure of colibactin-ICL. It revealed an α-ketoiminium in the central region of colibactin that likely serves as a key DNA recognition element, explaining colibactin’s sequence selectivity. A strand cleavage assay with high resolution LC-MS detection was used to study the site-specific products of various base sequences of 25mer double-strand DNA oligomer sequences containing colibactin ICLs. This data was used to understand how and when colibactin-ICLs form.