The Escherichia coli colibactin resistance protein ClbS is a novel DNA binding protein that protects DNA from nucleolytic degradation
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.
2019
2021-07-07 10:20:48
1033
ClbS, DNA-binding protein, DNA damage protection, pks genomic island, Escherichia coli
dk_c
Katja
Molan
70
Zdravko
Podlesek
70
Vesna
Hodnik
70
Matej
Butala
70
Eric
Oswald
70
Darja
Žgur-Bertok
70
UDK
4
579
ISSN pri članku
9
1568-7856
DOI
15
10.1016/j.dnarep.2019.05.003
COBISS_ID
3
5079119
RAZ_Molan_Katja_2019.pdf
787702
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2021-07-07 10:20:49