1887

Abstract

The DNA damage response of the multidrug-resistant pathogen , which induces mutagenic UmuD′C error-prone polymerases, differs from that of many bacteria. species lack a LexA repressor, but induce gene transcription after DNA damage. One regulator, UmuDAb, binds to and represses the promoters of the multiple ATCC 17978 alleles and the divergently transcribed and genes. is unique to the genus and of unknown function. 5' RACE (rapid amplification of cDNA ends) PCR mapping of the and transcriptional start sites revealed that their −35 promoter elements overlapped the UmuDAb binding site, suggesting that UmuDAb simultaneously repressed expression of both genes by blocking polymerase access. This coordinated control of and suggested that might also regulate DNA damage-inducible gene transcription. RNA-sequencing experiments in 17 978 cells showed that regulated approximately 25 % (=39) of the mitomycin C-induced regulon, with coregulating 17 of these -regulated genes. Eight genes (the polymerases, and ) were de-repressed in the absence of DNA damage, and nine genes were uninduced in the presence of DNA damage, in both and mutant strains. These data suggest has multiple roles, both as a co-repressor and as a positive regulator of DNA damage-inducible gene transcription. Additionally, 57 genes were induced by mitomycin C in the mutant but not in wild-type cells. This regulon contained multiple genes for DNA replication, recombination and repair, transcriptional regulators, RND efflux, and transport. This study uncovered another regulator of the atypical DNA damage response of this genus, to help describe how this pathogen acquires drug resistance through its expression of the error-prone polymerases under DdrR and UmuDAb control.

Keyword(s): repressor , DNA damage , SOS response , DdrR , UmuDAb and LexA
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2019-11-05
2019-12-14
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