Research News

Image of micronucleated HAP1 cells

When DNA is damaged, it remains in the cytoplasm instead of being incorporated into the nucleus during cell division and thus acts as an indicator of damage.

Credit: Osaka Metropolitan University

Colibactin is a small genotoxic molecule of polyketide produced by a subset of enteric bacteria including certain Escherichia coli (E. coli) harbored in the human gut microbiota. Its biosynthesis is governed by a multistep enzymatic process encoded by the polyketide synthase (pks) gene cluster. Colibactin is thought to exert its carcinogenic potential primarily through the induction of DNA interstrand crosslinks (ICLs); however, the precise mechanisms underlying its genotoxicity remain largely unresolved. In this study, a research team led by Osaka Metropolitan University focused on ICL formation and its associated repair pathways to investigate whether colibactin-induced ICLs play a central role in the induction of chromosomal aberrations and inhibition of cell proliferation.

HAP1 cells deficient in FANCD2, a gene essential for ICL repair, and their wild-type counterparts were infected with colibactin producing (clb⁺) E. coli strains isolated from a Japanese colorectal cancer (CRC) patient. Following recovery culture, the frequency of micronucleated (MN) cells was assessed. The results showed that FANCD2-deficient cells exhibited a significantly higher frequency of MN cells compared to wild-type cells. Additionally, the cytotoxicity of the clb⁺ strains was evaluated using the XTT assay. FANCD2-deficient cells demonstrated higher sensitivity to the clb⁺ E. coli strains than wild-type cells.

These findings suggest that colibactin, produced by clb⁺ E. coli, can play a role in the formation of ICLs, thereby contributing significantly to the induction of chromosomal aberrations and the inhibition of human cell proliferation.

Paper information

Journal: Genes and Environment
Title: DNA cross-link repair deficiency enhances human cell sensitivity to colibactin-induced genotoxicity  
DOI: 10.1186/s41021-025-00339-7
Authors: Masanobu Kawanishi, Osamu Tsubohira, Ai Ueshima, Yuuta Hisatomi, Yoshimitsu Oda, Michio Sato, Noriyuki Miyoshi, Michihiro Mutoh, Hideki Ishikawa, Keiji Wakabayashi, Takashi Yagi, Kenji Watanabe
Published: 22 September 2025
URL: https://doi.org/10.1186/s41021-025-00339-7

Contact

Masanobu Kawanishi
Graduate School of Science
Email: kawanishi-m[at]omu.ac.jp

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