Identification and characterization of the XRE family transcriptional regulator DdiA, a co-regulator of the DNA damage response in Myxococcus xanthus
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Abstract
Bacteria are remarkably adaptable, allowing them to survive and grow in every imaginable niche. In addition, they have to adapt to unfavorable environmental conditions in their natural habitats, such as oxidative stress, heat or cold stress, osmotic stress, nutrient limitation, anaerobic conditions, and antibiotic exposure. These adjustment processes are often mediated by the interaction of different regulatory networks that enable the bacteria to perceive extracellular chemical and physical stimuli and convert these into a specific response. At the end of this process, there is a targeted change in gene expression, enzyme activity and/or motility. Myxobacteria have evolved extraordinary strategies to adapt to their environment, including two motility systems, a complex life cycle, and interactions with other cells of the same species, predation, the production of secondary metabolites, and a large genome with numerous gene duplications. The Gram-negative, rod-shaped bacterium Myxococcus xanthus is the model organism for myxobacteria. In recent years, many of the systems used by M. xanthus have been deciphered; however, little is known about how it responds to DNA damage.
Using whole-cell proteomics, I have characterized the response of M. xanthus to the DNA-damaging agent mitomycin C (MMC). Remarkably, I found that several proteins involved in this response are upregulated independently of the LexA repressor, an almost universally conserved bacterial transcriptional regulator of genes encoding proteins of pathways involved in repairing DNA damage. Following up on these findings, I identified several DNA-binding proteins that were upregulated in response to MMC independently of LexA. Among these proteins, we focused on MXAN_0633 (from here on ddiA (DNA damage inducible protein A)). According to our proteomics data, DdiA specifically upregulates the error-prone trans-lesion DNA polymerase DnaE2. Furthermore, I demonstrated that the production of an active DdiA-mCherry fusion protein occurs heterogeneously. In the absence of exogenous DNA damage, only approximately 20% of cells expressed the fusion protein. However, upon DNA damage, the proportion of DdiA-mCherry positive cells increased dramatically, even without LexA. These findings strongly support the conclusion that DdiA is a component of the LexA-independent DNA damage response in M. xanthus.
While significant progress has been made in understanding the DNA damage response (DDR) in M. xanthus, many key questions remain unresolved. Although LexA and DdiA have been identified as important players, our findings suggest that additional transcription factors, yet to be characterized, contribute to the LexA-independent arm of the DDR. Identifying these regulators and their specific target genes will be essential for reconstructing the complete regulatory logic of the M. xanthus DDR.
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Issued: 2025-11-21
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Is based on: (DOI) 10.1128/jb.00184-25
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FB17:Biologie
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en
Keywords
DNA damageDNA repairDnaE2LexARecASOS responseXRE transcriptional regulatorerror-prone repairmitomycin Cmutagenic repair
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Jung, Jana: Identification and characterization of the XRE family transcriptional regulator DdiA, a co-regulator of the DNA damage response in Myxococcus xanthus. : 2025-11-21.
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