Redox signaling through zinc activates the radiation response in Deinococcus bacteria

AbstractDeinococcus bacteria are extremely resistant to radiation and other DNA damage- and oxidative stress-generating conditions. An efficient SOS-independent response mechanism inducing expression of several DNA repair genes is essential for this resistance, and is controlled by metalloprotease IrrE that cleaves and inactivates transcriptional repressor DdrO. Here, we identify the molecular signaling mechanism that triggers DdrO cleavage. We show that reactive oxygen species (ROS) stimulate the zinc-dependent metalloprotease activity of IrrE in Deinococcus. Sudden exposure of Deinococcus to zinc excess also rapidly induces DdrO cleavage, but is not accompanied by ROS production and DNA damage. Further, oxidative treatment leads to an increase of intracellular free zinc, indicating that IrrE activity is very likely stimulated directly by elevated levels of available zinc ions. We conclude that radiation and oxidative stress induce changes in redox homeostasis that result in IrrE activation by zinc in Deinococcus. We propose that a part of the zinc pool coordinated with cysteine thiolates is released due to their oxidation. Predicted regulation systems involving IrrE- and DdrO-like proteins are present in many bacteria, including pathogens, suggesting that such a redox signaling pathway including zinc as a second messenger is widespread and participates in various stress responses.

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Correction of ATM mutations in iPS cells from two ataxia-telangiectasia patients restores DNA damage and oxidative stress responses

Human Molecular Genetics ◽

10.1093/hmg/ddaa023 ◽

2020 ◽

Vol 29 (6) ◽

pp. 990-1001 ◽

Cited By ~ 5

Author(s):

Dmitry A Ovchinnikov ◽

Sarah L Withey ◽

Hannah C Leeson ◽

U Wang Lei ◽

Ashmitha Sundarrajan ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Stress Responses ◽

Ataxia Telangiectasia ◽

Compound Heterozygous ◽

Gene Correction ◽

Atm Kinase ◽

Atm Protein ◽

Induced Apoptosis ◽

And Oxidative Stress

Abstract Patients with ataxia-telangiectasia (A-T) lack a functional ATM kinase protein and exhibit defective repair of DNA double-stranded breaks and response to oxidative stress. We show that CRISPR/Cas9-assisted gene correction combined with piggyBac (PB) transposon-mediated excision of the selection cassette enables seamless restoration of functional ATM alleles in induced pluripotent stem cells from an A-T patient carrying compound heterozygous exonic missense/frameshift mutations, and from a patient with a homozygous splicing acceptor mutation of an internal coding exon. We show that the correction of one allele restores expression of ~ 50% of full-length ATM protein and ameliorates DNA damage-induced activation (auto-phosphorylation) of ATM and phosphorylation of its downstream targets, KAP-1 and H2AX. Restoration of ATM function also normalizes radiosensitivity, mitochondrial ROS production and oxidative-stress-induced apoptosis levels in A-T iPSC lines, demonstrating that restoration of a single ATM allele is sufficient to rescue key ATM functions. Our data further show that despite the absence of a functional ATM kinase, homology-directed repair and seamless correction of a pathogenic ATM mutation is possible. The isogenic pairs of A-T and gene-corrected iPSCs described here constitute valuable tools for elucidating the role of ATM in ageing and A-T pathogenesis.

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DNA damage and oxidative stress responses of mussels Mytilus galloprovincialis to paralytic shellfish toxins under warming and acidification conditions – Elucidation on the organ-specificity

Aquatic Toxicology ◽

10.1016/j.aquatox.2020.105619 ◽

2020 ◽

Vol 228 ◽

pp. 105619

Author(s):

Ana C. Braga ◽

Vitória Pereira ◽

Raquel Marçal ◽

Ana Marques ◽

Sofia Guilherme ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Stress Responses ◽

Mytilus Galloprovincialis ◽

Organ Specificity ◽

Shellfish Toxins ◽

Paralytic Shellfish Toxins ◽

Paralytic Shellfish ◽

Oxidative Stress Responses ◽

And Oxidative Stress

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Evaluation of DNA Damage and Oxidative Stress in Road Pavement Workers Occupationally Exposed to Polycyclic Aromatic Hydrocarbons

International Conference on Advances in Agricultural, Biological & Environmental Sciences (AABES-2014) Oct 15-16, 2014 Dubai (UAE) ◽

10.15242/iicbe.c1014023 ◽

2014 ◽

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Polycyclic Aromatic Hydrocarbons ◽

Aromatic Hydrocarbons ◽

Road Pavement ◽

Occupationally Exposed ◽

Polycyclic Aromatic ◽

And Oxidative Stress

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Repressive effect of Rhus coriaria L. fruit extracts on microglial cells-mediated inflammatory and oxidative stress responses

Journal of Ethnopharmacology ◽

10.1016/j.jep.2020.113748 ◽

2021 ◽

Vol 269 ◽

pp. 113748

Author(s):

Mohamad Khalil ◽

Ali Bazzi ◽

Dana Zeineddine ◽

Wissam Jomaa ◽

Ahmad Daher ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Responses ◽

Microglial Cells ◽

Fruit Extracts ◽

Repressive Effect ◽

Rhus Coriaria ◽

Oxidative Stress Responses ◽

And Oxidative Stress

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Impact of Zinc Excess on Germination, Growth Parameters and Oxidative Stress of Sweet Basil (Ocimum basilicum L.)

Bulletin of Environmental Contamination and Toxicology ◽

10.1007/s00128-021-03188-6 ◽

2021 ◽

Author(s):

Hela Mahmoudi ◽

Imene Ben Salah ◽

Wafa Zaouali ◽

Walid Zorrig ◽

Ameni Smaoui ◽

...

Keyword(s):

Oxidative Stress ◽

Growth Parameters ◽

Ocimum Basilicum ◽

Sweet Basil ◽

Zinc Excess ◽

And Oxidative Stress

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Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03756-3 ◽

2021 ◽

Author(s):

Sinan Xiong ◽

Wee-Joo Chng ◽

Jianbiao Zhou

Keyword(s):

Oxidative Stress ◽

Multiple Myeloma ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Cell Fate ◽

Stress Responses ◽

Plasma Cells ◽

Reactive Oxygen Species Generation ◽

Future Research ◽

And Oxidative Stress

AbstractUnder physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising from immunoglobulin-secreting plasma cells. MM cells are subject to continual ER stress and highly dependent on the UPR signaling activation due to overproduction of paraproteins. Mounting evidence suggests the close linkage between ER stress and oxidative stress, demonstrated by overlapping signaling pathways and inter-organelle communication pivotal to cell fate decision. Imbalance of intracellular homeostasis can lead to deranged control of cellular functions and engage apoptosis due to mutual activation between ER stress and reactive oxygen species generation through a self-perpetuating cycle. Here, we present accumulating evidence showing the interactive roles of redox homeostasis and proteostasis in MM pathogenesis and drug resistance, which would be helpful in elucidating the still underdefined molecular pathways linking ER stress and oxidative stress in MM. Lastly, we highlight future research directions in the development of anti-myeloma therapy, focusing particularly on targeting redox signaling and ER stress responses.

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