The Fanconi anemia pathway repairs colibactin-induced DNA interstrand cross-links.

ABSTRACT: Colibactin is a secondary metabolite produced by bacteria present in the human gut and is implicated in the development of colorectal cancer. This genotoxin alkylates deoxyadenosines on opposite strands of host cell DNA to produce DNA interstrand cross-links. While cells have evolved multiple mechanisms to resolve ("unhook") interstrand cross-links, little is known about which of these pathways promote resistance to colibactin. Here, we use Xenopus egg extracts to investigate replication-coupled repair of colibactin-induced interstrand cross-links. We show that replication fork stalling at a colibactin-induced interstrand cross-link activates the Fanconi anemia interstrand cross-link repair pathway, which unhooks the interstrand cross-link through nucleolytic incisions. These incisions gen

SUBMITTER: Altshuller M 

PROVIDER: S-EPMC12657977 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature