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The Escherichia coli colibactin resistance protein ClbS is a novel DNA binding protein that protects DNA from nucleolytic degradation
ID Molan, Katja (Author), ID Podlesek, Zdravko (Author), ID Hodnik, Vesna (Author), ID Butala, Matej (Author), ID Oswald, Eric (Author), ID Žgur-Bertok, Darja (Author)

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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.

Language:English
Keywords:ClbS, DNA-binding protein, DNA damage protection, pks genomic island, Escherichia coli
Work type:Article (dk_c)
Typology:1.01 - Original Scientific Article
Organization:BF - Biotechnical Faculty
Year:2019
Publication status in journal:Published
Article version:Publisher's version of article
Number of pages:Str. 50-54
Numbering:Vol. 79
PID:20.500.12556/RUL-128248 This link opens in a new window
UDC:579
ISSN on article:1568-7856
DOI:10.1016/j.dnarep.2019.05.003 This link opens in a new window
COBISS.SI-ID:5079119 This link opens in a new window
Publication date in RUL:07.07.2021
Views:372
Downloads:101
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Record is a part of a journal

Title:DNA Repair
Publisher:Elsevier
ISSN:1568-7856
COBISS.SI-ID:24102405 This link opens in a new window

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

Projects

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Project number:P1-0198
Name:Molekularno-biološke raziskave mikroorganizmov

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Project number: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
Funding programme:PhD grant

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