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Scientists Reveal How Gut Toxin Colibactin Cross-Links DNA in Colorectal Cancer

A Science study captures the unstable molecule bound to AT-rich sites in the DNA minor groove, offering a clear mechanism for the mutation patterns seen in patient tumors.

Overview

  • Researchers produced colibactin in situ with live bacteria and resolved the DNA-bound structure using mass spectrometry and NMR.
  • The toxin forms interstrand cross-links that lock the two DNA strands together, creating highly toxic lesions that can yield characteristic mutations.
  • Colibactin preferentially targets AT-rich sequences within the DNA minor groove rather than damaging the genome at random.
  • The structure features a positively charged core and twin reactive warheads that drive sequence recognition and covalent binding.
  • The findings strengthen the mechanistic link to a measurable subset of colorectal cancers reported in roughly 5–20% of cases and point to potential diagnostics, treatments, and microbiome-based prevention.