dinB

The WYL domain is a nucleotide-sensing module that controls the activity of transcription factors involved in the regulation of DNA damage response and phage defense mechanisms in bacteria. In this study, we investigated a WYL domain-containing transcription factor in Mycobacterium smegmatis that we termed stress-involved WYL domain-containing regulator (SiwR). We found that SiwR controls adjacent genes that belong to the DinB/YfiT-like putative metalloenzymes superfamily by upregulating their expression in response to various genotoxic stress conditions, including upon exposure to H2 O2 or the natural antibiotic zeocin...

Selenoneine (SEN) is a natural histidine derivative with radical-scavenging activity and shows higher antioxidant potential than its sulfur-containing isolog ergothioneine (EGT). Recently, the SEN biosynthetic pathway in Variovorax paradoxus was reported. Resembling EGT biosynthesis, the committed step of SEN synthesis is catalyzed by a nonheme Fe-dependent oxygenase termed SenA. This enzyme catalyzes oxidative carbon‑selenium (CSe) bond formation to conjugate N-α-trimethyl histidine (TMH) and selenosugar to yield selenoxide; the process parallels the EGT biosynthetic route, in which sulfoxide synthases known as EgtB members catalyze the conjugation of TMH and cysteine or γ-glutamylcysteine to afford sulfoxides...

We investigated the role(s) of the damage-inducible SOS response dinB and imuBC gene products in the generation of ciprofloxacin-resistance mutations in the important human opportunistic bacterial pathogen, Pseudomonas aeruginosa. We found that the overall numbers of ciprofloxacin resistant (CipR ) mutants able to be recovered under conditions of selection were significantly reduced when the bacterial cells concerned carried a defective dinB gene, but could be elevated to levels approaching wild-type when these cells were supplied with the dinB gene on a plasmid vector; in turn, firmly establishing a role for the dinB gene product, error-prone DNA polymerase IV, in the generation of CipR mutations in P...

In order to cope with the risk of stress-induced mutagenesis, cells in all kingdoms of life employ Y-family DNA polymerases to resolve resulting DNA lesions and thus maintaining the integrity of the genome. In Escherichia coli, the DNA polymerase IV, or DinB, plays this crucial role in coping with these type of mutations via the so-called translesion DNA synthesis. Despite the availability of several high-resolution crystal structures, important aspects of the functional repertoire of DinB remain elusive...

Translesion synthesis by translesion polymerases is a conserved mechanism of DNA damage tolerance. In bacteria, DinB enzymes are the widely distributed promutagenic translesion polymerases. The role of DinBs in mycobacterial mutagenesis was unclear until recent studies revealed a role for mycobacterial DinB1 in substitution and frameshift mutagenesis, overlapping with that of translesion polymerase DnaE2. Mycobacterium smegmatis encodes two additional DinBs (DinB2 and DinB3) and Mycobacterium tuberculosis encodes DinB2, but the roles of these polymerases in mycobacterial damage tolerance and mutagenesis is unknown...

Overuse of antimicrobial agents are generally considered to be a key factor in the occurrence of antibiotic resistance bacteria (ARB). Nevertheless, it is unclear whether ARB can be induced by non-antibiotic chemicals such as nonsteroidal anti-inflammatory drug (NSAID). Thus, the objective of this study is to investigate whether NSAID diclofenac (DCF) promote the emergence of antibiotic resistance in Escherichia coli K12 MG1655. Our results suggested that DCF induced the occurrence of ARB which showed hereditary stability of resistance...

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The clustering of mutations observed in cancer cells is reminiscent of the stress-induced mutagenesis (SIM) response in bacteria. Bacteria deploy SIM when faced with DNA double-strand breaks in the presence of conditions that elicit an SOS response. SIM employs DinB , the evolutionary precursor to human trans-lesion synthesis (TLS) error-prone polymerases, and results in mutations concentrated around DNA double-strand breaks with an abundance that decays with distance. We performed a quantitative study on single nucleotide variant calls for whole-genome sequencing data from 1950 tumors, non-inherited mutations from 129 normal samples, and acquired mutations in 3 cell line models of stress-induced adaptive mutation...

Antibiotic resistance of Mycobacterium tuberculosis is exclusively a consequence of chromosomal mutations. Translesion synthesis (TLS) is a widely conserved mechanism of DNA damage tolerance and mutagenesis, executed by translesion polymerases such as DinBs. In mycobacteria, DnaE2 is the only known agent of TLS and the role of DinB polymerases is unknown. Here we demonstrate that, when overexpressed, DinB1 promotes missense mutations conferring resistance to rifampicin, with a mutational signature distinct from that of DnaE2, and abets insertion and deletion frameshift mutagenesis in homo-oligonucleotide runs...

Escherichia coli is a commensal bacterium and one of the first bacteria to colonize the digestive tract of newborns after birth. It is characterized by great versatility and metabolic flexibility that allows its survival in different niches. The present study aims at analyzing the diversity of E. coli strains isolated from the intestinal microbiota of children aged from 0 to 5 years in the commune of Abomey-Calavi in Benin. For this purpose, a descriptive and analytical cross-sectional study was conducted. A total of 135 stool samples were collected from the pediatric clinic of Abomey-Calavi...

Y-family DNA polymerases, unlike replicative DNA polymerases, are enzymes characterized by their ability to bypass DNA lesions and continue extension of damaged DNA via Translesion Synthesis (TLS). One such polymerase, human polymerase kappa (Pol κ), can efficiently bypass minor groove adducts, most notably N2 -furfuryl-deoxy-guanosine (N2- ffdG), but it is inhibited by major groove adducts such as O6 -methylated-deoxy-guanosine (O6- Met-dG). Pol k is composed of five domains including its novel N-clasp domain, as well as the thumb, palm, fingers, and little finger (polymerase associated domain or PAD) domains which are found across Y-family polymerases...

Y-family DNA polymerases are a class of error-prone polymerases able to perform DNA translesion synthesis. E. coli DNA Polymerase IV (also called DinB from the name of the gene) is a Y-family DNA polymerase implicated in stress-induced mutagenesis. As other DNA polymerases, DinB has the general architecture of a right hand, with palm, thumb, and fingers subdomains. In addition, Y-family polymerases have an extra domain, namely the "little finger" or polymerase-associated domain (PAD) and have a more solvent accessible active-site than their high-fidelity replicative counterparts...

To cope with stressful conditions, including antibiotic exposure, bacteria activate the SOS response, a pathway that induces error-prone DNA repair and mutagenesis mechanisms. In most bacteria, the SOS response relies on the transcriptional repressor LexA and the co-protease RecA, the latter being also involved in homologous recombination. The role of the SOS response in stress- and antibiotic-induced mutagenesis has been characterized in detail in the model organism Escherichia coli . However, its effect on antibiotic resistance in the human pathogen Pseudomonas aeruginosa is less clear...

Y-family DNA polymerases (pols) consist of six phylogenetically separate subfamilies; two UmuC (polV) branches, DinB (pol IV, Dpo4, polκ), Rad30A/POLH (polη), and Rad30B/POLI (polι) and Rev1. Of these subfamilies, DinB orthologs are found in all three domains of life; eubacteria, archaea, and eukarya. UmuC orthologs are identified only in bacteria, whilst Rev1 and Rad30A/B orthologs are only detected in eukaryotes. Within eukaryotes, a wide array of evolutionary diversity exists. Humans possess all four Y-family pols (pols η, ι, κ, and Rev1), Schizosaccharomyces pombe has three Y-family pols (pols η, κ, and Rev1), and Saccharomyces cerevisiae only has polη and Rev1...

The DNA polymerase Polκ plays a key role in translesion synthesis, an error-prone replication mechanism. Polκ is overexpressed in various tumor types. Here, we found that melanoma and lung and breast cancer cells experiencing stress from oncogene inhibition up-regulated the expression of Polκ and shifted its localization from the cytoplasm to the nucleus. This effect was phenocopied by inhibition of the kinase mTOR, by induction of ER stress, or by glucose deprivation. In unstressed cells, Polκ is continually transported out of the nucleus by exportin-1...

The E. coli system of Cairns and Foster employs a lac frameshift mutation that reverts rarely (10-9 /cell/division) during unrestricted growth. However, when 108 cells are plated on lactose medium, the non-growing lawn produces ∼50 Lac+ revertant colonies that accumulate linearly with time over 5 days. Revertants carry very few associated mutations. This behavior has been attributed to an evolved mechanism (" adaptive mutation " or " stress-induced mutagenesis ") that responds to starvation by preferentially creating mutations that improve growth...

Spontaneous mutations are important players in evolution. Nevertheless, there is a paucity of information about the mutagenic processes operating in most bacterial species. In this work, we implemented two forward mutational markers for studies in Caulobacter crescentus. We confirmed previous results in which A:T→ G:C transitions are the most prevalent type of spontaneous base substitutions in this organism, although there is considerable deviation from this trend in one of the loci analyzed. We also investigated the role of dinB and imuC, encoding error-prone DNA polymerases, in spontaneous mutagenesis in this GC-rich organism...

Deinococcus radiodurans is an extremophilic bacterium well-known for its extraordinary resistance to ionizing radiation and other DNA damage- and oxidative stress-generating agents. In addition to its efficient DNA damage repair and oxidative stress resistance mechanisms, protein family expansions and stress-induced genes/proteins are also regarded as important components that add to the robustness of this bacterium. D. radiodurans encodes specific expansions of 13 DinB/YfiT homologs, which is a relatively large number when compared to those found in Gram-positive bacteria...

Bacterial Y-family DNA polymerases are usually classified into DinB (Pol IV), UmuC (the catalytic subunit of Pol V) and ImuB, a catalytically dead essential component of the ImuA-ImuB-DnaE2 mutasome. However, the true diversity of Y-family polymerases is unknown. Furthermore, for most of them the structures are unavailable and interactions are poorly characterized. To gain a better understanding of bacterial Y-family DNA polymerases, we performed a detailed computational study. It revealed substantial diversity, far exceeding traditional classification...

The evolutionarily conserved Escherichia coli translesion DNA Polymerase IV (DinB) is one of three enzymes that can bypass potentially deadly DNA lesions on the template strand during DNA replication. Remarkably, however, DinB is the only known translesion DNA polymerase active in RecA-mediated strand exchange during error-prone double strand break repair. In this process, a ssDNA-RecA nucleoprotein filament invades homologous dsDNA, pairing the ssDNA with the complementary strand in the dsDNA. When exchange reaches the 3' end of the ssDNA, a DNA polymerase can add nucleotides onto the end, using one strand of dsDNA as a template and displacing the other...