The Escherichia coli colibactin resistance protein ClbS is a novel DNA binding protein that protects DNA from nucleolytic degradation

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

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.

• Language: English
• Keywords: ClbS, DNA-binding protein, DNA damage protection, pks genomic island, Escherichia coli
• Work type: Article (dk_c)
• Tipology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty
• Year: 2019
• Number of pages: Str. 50-54
• Numbering: Vol. 79
• UDC: 579
• ISSN on article: 1568-7856
• DOI: 10.1016/j.dnarep.2019.05.003
• COBISS.SI-ID: 5079119
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Record is a part of a journal

• Title: DNA Repair
• Publisher: Elsevier
• ISSN: 1568-7856
• COBISS.SI-ID: 24102405

Document is financed by a project

• Funder: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
• Project no.: P1-0198
• Name: Molekularno-biološke raziskave mikroorganizmov

• Funder: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
• Project no.: J1-8150
• Name: "DNA sampling II":": Metoda za prepoznavo na DNA neposredno ali posredno vezanih proteinov v bakteriji

• Funder: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
• Funding Programme: PhD grant

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.07.2019