Evolution of YacG to safeguard DNA gyrase from external perturbation

Biswas, P and Sengupta, S and Nagaraja, V (2023) Evolution of YacG to safeguard DNA gyrase from external perturbation. In: Research in Microbiology, 174 (7).

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Abstract

Cells have evolved strategies to safeguard their genome integrity. We describe a mechanism to counter double strand breaks in the chromosome that involves the protection of an essential housekeeping enzyme from external agents. YacG is a DNA gyrase inhibitory protein from Escherichia coli that protects the bacterium from the cytotoxic effects of catalytic inhibitors as well as cleavage-complex stabilizers of DNA gyrase. By virtue of blocking the primary DNA binding site of the enzyme, YacG prevents the accumulation of double strand breaks induced by gyrase poisons. It also enables the bacterium to resist the growth-inhibitory property of novobiocin. Gyrase poison-induced oxidative stress upregulates YacG production, probably as a cellular response to counter DNA damage. YacG-mediated protection of the genome is specific for gyrase targeting agents as the protection is not observed from the action of general DNA damaging agents. YacG also intensifies the transcription stress induced by rifampicin substantiating the importance of gyrase activity during transcription. Although essential for bacterial survival, DNA gyrase often gets entrapped by external inhibitors and poisons, resulting in cell death. The existence of YacG to specifically protect an essential housekeeping enzyme might be a strategy adopted by bacteria for competitive fitness advantage. © 2023 Institut Pasteur

Item Type:	Journal Article
Publication:	Research in Microbiology
Publisher:	Elsevier Masson s.r.l.
Additional Information:	The copyright for this article belongs to the Elsevier Masson s.r.l.
Keywords:	beta galactosidase; DNA topoisomerase (ATP hydrolysing); double stranded DNA; gyrase inhibitor; protein yacg; unclassified drug, Article; bacterial gene; bacterial genome; bacterial strain; bacterial survival; bacteriostasis; cell death; comparative study; complex formation; cytotoxicity; DNA damage; DNA replication; DNA transcription; Escherichia coli; gel mobility shift assay; genetic code; Haemophilus; Haemophilus influenzae; housekeeping gene; lacz gene; molecular evolution; nonhuman; oxidative stress; promoter region; Sinorhizobium meliloti; upregulation
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	24 Nov 2023 05:37
Last Modified:	24 Nov 2023 05:37
URI:	https://eprints.iisc.ac.in/id/eprint/83239

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