Katja Molan (Author), Zdravko Podlesek (Author), Vesna Hodnik (Author), Matej Butala (Author), Eric Oswald (Author), Darja Žgur-Bertok (Author)

Abstract

Cells employ specific and nonspecific mechanisms to protect their genome integrity against exogenous and endogenous factors. The clbS gene is part of the polyketide synthase machinery (pks genomic island) encoding colibactin, a genotoxin implicated in promoting colorectal cancer. The pks is found among the Enterobacteriaceae, in particular Escherichia coli strains of the B2 phylogenetic group. Several resistance mechanisms protect toxin producers against toxicity of their products. ClbS, a cyclopropane hydrolase, was shown to confer colibactin resistance by opening its electrophilic cyclopropane ring. Here we report that ClbS sustained viability and enabled growth also of E. coli expressing another genotoxin, the Usp nuclease. The recA::gfp reporter system showed that ClbS protects against Usp induced DNA damage. To elucidate the mechanism of ClbS mediated protection, we studied the DNA binding ability of the ClbS protein. We show that ClbS directly interacts with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), whereas ssDNA seems to be the preferred substrate. Thus, the ClbS DNA-binding characteristics may serve bacteria to protect their genomes against DNA degradation.

Keywords

clbS;DNA-binding protein;DNA damage protection;pks genomic island;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL BF - Biotechnical Faculty
UDC: 579
COBISS: 5079119 Link will open in a new window
ISSN: 1568-7856
Views: 267
Downloads: 62
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Other data

Secondary keywords: Escherichia coli;
Type (COBISS): Article
Pages: str. 50-54
Issue: ǂVol. ǂ79
Chronology: 2019
DOI: 10.1016/j.dnarep.2019.05.003
ID: 13112574