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Lookup NU author(s): Dr Kathy StrattonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
DNA damage triggers a widely conserved stress response in bacteria called the SOS response, which involves two key regulators, the activator RecA and the transcriptional repressor LexA. Despite the wide conservation of the SOS response, the number of genes controlled by LexA varies considerably between different organisms. The filamentous soil-dwelling bacteria of the genus Streptomyces contain LexA and RecA homologs, but their roles in Streptomyces have not been systematically studied. Here, we demonstrate that RecA and LexA are required for the survival of Streptomyces venezuelae during DNA-damaging conditions and for normal development during unperturbed growth. Monitoring the activity of a fluorescent recA promoter fusion and LexA protein levels revealed that the activation of the SOS response is delayed in S. venezuelae. By combining global transcriptional profiling and chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we determined the LexA regulon and defined the core set of DNA damage repair genes that are expressed in response to treatment with the DNA-alkylating agent mitomycin C. Our results show that DNA damage-induced degradation of LexA results in the differential regulation of LexA target genes. Using surface plasmon resonance, we further confirmed the LexA DNA binding motif (SOS box) and demonstrated that LexA displays tight but distinct binding affinities to its target promoters, indicating a graded response to DNA damage. IMPORTANCE The transcriptional regulator LexA functions as a repressor of the bacterial SOS response, which is induced under DNA-damaging conditions. This results in the expression of genes important for survival and adaptation. Here, we report the regulatory network controlled by LexA in the filamentous antibiotic-producing Streptomyces bacteria and establish the existence of the SOS response in Streptomyces. Collectively, our work reveals significant insights into the DNA damage response in Streptomyces that will promote further studies to understand how these important bacteria adapt to their environment.
Author(s): Stratton KJ, Bush MJ, Chandra G, Stevenson CEM, Findlay KC, Schlimpert S
Publication type: Article
Publication status: Published
Journal: Journal of Bacteriology
Year: 2022
Volume: 204
Issue: 8
Print publication date: 01/08/2022
Online publication date: 13/07/2022
Acceptance date: 27/06/2022
Date deposited: 23/08/2024
ISSN (electronic): 1098-5530
Publisher: American Society for Microbiology
URL: https://doi.org/10.1128/jb.00108-22
DOI: 10.1128/jb.00108-22
Data Access Statement: The authors confirm that all supporting data have been provided within the article or through supplementaly data files. Raw RNA-seq and ChIP-seq data have been deposited in the MIAME-compliant ArrayExpress database (https://www.ebi.ac.uk/arrayexpress/) under accession no. E-MTAB-11556 and E-MTAB-11603.
PubMed id: 35862789
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