Effect of Rv2282c, Rv1990c and Rv1985c overexpression on gene expression under ATc induction in Mycobacterium smegmatis [batch 1]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mycolicibacterium smegmatis
PROVIDER: GSE327825 | GEO | 2026/05/26
REPOSITORIES: GEO
Similar Datasets
Project description:transcriptional regulation on DNA damage response is essential for persistence and mutagenesis of Mtb. Rv3574, Rv0047c and Rv0602c are conducted as control regulators with comparison to Rv2282c, Rv1990c and Rv1985c. We here report Rv3574, Rv0047c and Rv0602c inhibit cell division but show no influence on DNA damage response system compared to Rv2282c, Rv1990c and Rv1985c. Overexpression of Rv3574, Rv0047c and Rv0602c does not influence the expression of genes related to oxidative stress. Complemention of tpx does not relieve the effect of Rv3574, Rv0047c and Rv0602c. Taken together, our study provides a conceptual framework for understanding how mycobacteria orchestrate the complex DDR system through redox-based transcriptional regulation.
2026-05-26 | GSE327827 | GEO
Project description:Mycothiol (AcCys-GlcN-Ins, MSH) is the major thiol-redox buffer in Actinomycetes, including Mycobacterium and Corynebacterium species. ). Protein S-mycothiolation controls the activities of several redox enzymes that function in detoxification of ROS and methionine sulfoxides, including the thiol peroxidase Tpx, the mycothiol peroxidase Mpx and the methionine sulfoxide reductase MsrA. Here we investigated the level of protein S-mycothiolation in Mycobacterium smegmatis under oxidative stress as well as its NaOCl stress response.
2017-06-30 | PXD003303 | Pride
Project description:We examined the DNA damage response of bacterium E. coli using the replication inhibitor azidothyimdine (AZT), and RNA-Seq analysis. We confirm the induction of classic SOS loci by AZT and identify several genes, including many of the pyrimidine pathway, that are induced dependent on LexA cleavage, but have not been previously demonstrated to be DNA damage-inducible. Despite a strong dependence on LexA, these genes lack LexA boxes and their regulation by LexA is likely to be indirect via unknown factors. We show that stringent starvation protein, SspA, is as important as LexA in the regulation of AZT-induced genes. Our experiments identify a new set of LexA-independent DNA damage inducible genes, including 22 small RNA genes, some of which appear to activated by SspA. Motility and chemotaxis genes are strongly down-regulated by AZT, possibly as a result of one of more of the small RNAs or other transcription factors such as AppY and GadE, whose expression is elevated by AZT. Genes controlling the iron siderophore, enterobactin, and iron homeostasis are also strongly induced, independent of LexA. We confirm that IraD anti-adaptor protein and its upstream genes are induced, independent of LexA and that a second anti-adaptor, IraM is also strongly AZT-inducible, independent of LexA, suggesting that RpoS stabilization via these anti-adaptor proteins is an integral part of DNA damage tolerance.
2024-06-26 | GSE263906 | GEO
Project description:Repair of DNA damage is essential for genome integrity. DNA damage elicits a DNA damage response (DDR) that includes error-free and error-prone, i.e. mutagenic, repair. The SOS response is a widely conserved system in bacteria that regulates the DDR and depends on the recombinase RecA and the transcriptional repressor LexA. However, RecA/LexA-independent DDRs have been identified in several bacterial species. Here, using a whole-cell, label-free quantitative proteomics approach, we map the proteomic response in Myxococcus xanthus to mitomycin C treatment and the lack of LexA. In doing so, we confirm a LexA-independent DDR in M. xanthus. Using a candidate approach, we identify DdiA, a transcriptional regulator of the XRE family, and demonstrate that it regulates a subset of the LexA-independent DDR genes. Further, we show that ddiA expression is activated heterogeneously in a subpopulation of cells in the absence of exogenous genotoxic stress and is reversibly activated population-wide in response to such stress. We show that DdiA, indirectly or directly, activates the expression of dnaE2, which encodes the DnaE2 error-prone DNA polymerase, and inhibits the expression of recX, which encodes RecX, a negative regulator of RecA. Accordingly, the ΔddiA mutant has a lower mutation frequency than the wild-type but also a fitness defect, suggesting that DdiA mediates a trade-off between fitness and mutagenesis. We speculate that the DdiA-dependent response is tailored to counter replication stress, thereby preventing the induction of the complete RecA/LexA-dependent DDR in the absence of exogenous genotoxic stress.
2025-02-12 | PXD060688 | Pride
Project description:Suppression of the SOS response in combination with drugs has been proposed as a potential target to tackle antimicrobial resistance. The SOS response is the pathway used to repair bacterial DNA damage induced by antimicrobials such as quinolones. The extent of lexA-regulated protein expression and other associated systems under pressure of agents that damage bacterial DNA in clinical isolates remains unclear. The aim of this study was to assess the impact of this strategy on the proteome profile of Escherichia coli clinical strains.
2024-04-04 | PXD050358 | Pride
Project description:Our results indicate that the transcriptional responses to HPUra, MMC, and UV are only partially overlapping. recA is the major transcriptional regulator under all of the tested conditions and LexA appears to directly repress expression of 63 genes in 26 operons, including the 18 operons previously identified as LexA targets. MMC and HPUra treatments caused induction of an integrative and conjugative element (ICEBs1) and resident prophages (PBSX and SPß), which affected expression of many host genes. Consistent with previous results, induction of these mobile elements required recA. Induction of the phage appeared to require inactivation of LexA. Unrepaired UV damage and treatment with MMC also affected expression of some of the genes that are controlled by DnaA. Furthermore, MMC treatment caused an increase in origin proximal gene dosage Keywords: time dependent DNA damage response
2006-04-18 | GSE4673 | GEO
Project description:Shimoni2009 - Escherichia Coli SOS
Simple model, involving only the basic components of the circuit, sufficient to explain the peaks in the promoter activities of recA and lexA.
This model is described in the article:
Stochastic analysis of the SOS response in Escherichia coli.
Shimoni Y, Altuvia S, Margalit H, Biham O
PloS one. 2009; 4(5):e5363
Abstract:
BACKGROUND: DNA damage in Escherichia coli evokes a response mechanism called the SOS response. The genetic circuit of this mechanism includes the genes recA and lexA, which regulate each other via a mixed feedback loop involving transcriptional regulation and protein-protein interaction. Under normal conditions, recA is transcriptionally repressed by LexA, which also functions as an auto-repressor. In presence of DNA damage, RecA proteins recognize stalled replication forks and participate in the DNA repair process. Under these conditions, RecA marks LexA for fast degradation. Generally, such mixed feedback loops are known to exhibit either bi-stability or a single steady state. However, when the dynamics of the SOS system following DNA damage was recently studied in single cells, ordered peaks were observed in the promoter activity of both genes (Friedman et al., 2005, PLoS Biol. 3(7):e238). This surprising phenomenon was masked in previous studies of cell populations. Previous attempts to explain these results harnessed additional genes to the system and deployed complex deterministic mathematical models that were only partially successful in explaining the results.
PRINCIPAL FINDINGS: Here we apply stochastic methods, which are better suited for dynamic simulations of single cells. We show that a simple model, involving only the basic components of the circuit, is sufficient to explain the peaks in the promoter activities of recA and lexA. Notably, deterministic simulations of the same model do not produce peaks in the promoter activities.
SIGNIFICANCE: We conclude that the double negative mixed feedback loop with auto-repression accounts for the experimentally observed peaks in the promoter activities. In addition to explaining the experimental results, this result shows that including additional regulations in a mixed feedback loop may dramatically change the dynamic functionality of this regulatory module. Furthermore, our results suggests that stochastic fluctuations strongly affect the qualitative behavior of important regulatory modules even under biologically relevant conditions, thus emphasizing the importance of stochastic analysis of regulatory circuits.
This model is hosted on BioModels Database and identified by: MODEL2937159804.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.
2005-01-01 | MODEL2937159804 | BioModels
Project description:The SOS response is a conserved pathway that is activated under certain stress conditions and is regulated by the repressor LexA and the activator RecA. The food-borne pathogen Listeria monocytogenes contains RecA and LexA homologs, but their roles in Listeria have not been established. In this study, we identified the SOS regulon in L. monocytogenes by comparing the transcription profiles of the wild-type strain and the ΔrecA mutant strain after exposure to the DNA damaging agent mitomycinC (MMC). The SOS response is an inducible pathway involved in DNA repair, restart of stalled replication forks, and in induction of genetic variation in stressed and stationary phase cells. It is regulated by LexA and RecA. LexA is an autoregulatory repressor which binds to a consensus sequence in the promoter region of the SOS response genes, thereby repressing transcription. A consensus LexA binding motif for L. monocytogenes has not been identified thus far. Generally, the SOS response is induced under circumstances in which single stranded DNA accumulates in the cell. This results in activation of RecA, which in turn stimulates cleavage of LexA, and ultimately in the induction of the SOS response. Keywords: stress response, loop design, SOS response, mitomycin c, listeria monocytogenes, RecA, LexA
2009-11-25 | GSE12634 | GEO
Project description:Bacteria encode for gene regulatory networks crucial for sensing and repairing DNA damage. Upon exposure to genotoxic stress, these transcriptional networks are induced in a temporally structured manner. A case in point is of the highly conserved SOS response that is regulated by the LexA repressor. Studies have proposed that affinity of LexA towards promoters of SOS response genes is the primary determinant of its expression dynamics. Here, we describe an additional level of regulation beyond LexA properties that modulates the SOS response gene expression pattern. Using transcriptomic analyses, we reveal a distinct temporal hierarchy in the induction of SOS-regulated genes in Caulobacter crescentus. We observe that LexA properties are insufficient in predicting the temporal hierarchy of these genes. Instead, we find that intrinsic promoter strength underlies the order of gene activation, with differential sigma factor association as a key factor in modulating gene expression timing. Our findings highlight a novel regulatory layer in SOS dynamics and underscore the importance of promoter properties in shaping bacterial stress responses.
2025-11-26 | GSE311073 | GEO
Project description:Mycolicibacterium (Mycobacterium) smegmatis DNA repair mutants and their sensitivity to oxidative damage.
| PRJNA675073 | ENA