Genome-scale CRISPR/Cas9 screening reveals the role of <i>PSMD4</i> in colibactin-mediated cell cycle arrest.

ABSTRACT: Colibactin is a genotoxic secondary metabolite produced by certain Enterobacteriaceae strains that populate the intestine and produces a specific mutational signature in human colonocytes. However, the host pathways involved in colibactin response remain unclear. To address this gap, we performed genome-wide CRISPR/Cas9 knockout screens and RNA sequencing utilizing live pks⁺ bacteria and a synthetic colibactin analog. We identified 20 enriched genes with a MAGeCK score of >2.0 in both screens, including proteasomal subunits (e.g., PSMG4 and PSMD4), RNA processing factors (e.g., SF1 and PRPF8), and RNA polymerase III (e.g., CRCP), and validated the role of PSMD4 in colibactin sensitization. PSMD4 knockout in HEK293T a

SUBMITTER: Dougherty MW 

PROVIDER: S-EPMC11934320 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature