Molecular Analysis of Carbon Ion-Induced Mutations in DNA Repair-Deficient Strains of Saccharomyces cerevisiae

Matuo, Youichirou; Izumi, Yoshinobu; Sakamoto, Ayako; Hase, Yoshihiro; Satoh, Katsuya; Shimizu, Kikuo

doi:10.3390/qubs3030014

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…A transcriptomic and functional genetic analysis of Deinococcus radiodurans produced the same result [ 65 ]. Moreover, induction of RAD52 after irradiation is observed in S. cerevisiae [ 77 ] and in E. dermatitidis [ 9 , 41 ], but the regulation of its expression, or of RAD54 , do not appear to be required for them to carry out their normal functions [ 55 , 78 ], and the transcriptomic response (e.g., induction of DNA repair proteins, inhibition of growth) is either largely similar across many organisms of varying sensitivity to γ-radiation [ 66 , 77 , 79 , 80 , 81 ], or has been shown not to assist in the identification of DNA repair genes at all [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomics Reveals Distinct Changes Associated with Increased Gamma Radiation Resistance in the Black Yeast Exophiala dermatitidis

Schultzhaus

Romsdahl

et al. 2020

Genes

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The yeast Exophiala dermatitidis exhibits high resistance to γ-radiation in comparison to many other fungi. Several aspects of this phenotype have been characterized, including its dependence on homologous recombination for the repair of radiation-induced DNA damage, and the transcriptomic response invoked by acute γ-radiation exposure in this organism. However, these findings have yet to identify unique γ-radiation exposure survival strategies—many genes that are induced by γ-radiation exposure do not appear to be important for recovery, and the homologous recombination machinery of this organism is not unique compared to more sensitive species. To identify features associated with γ-radiation resistance, here we characterized the proteomes of two E. dermatitidis strains—the wild type and a hyper-resistant strain developed through adaptive laboratory evolution—before and after γ-radiation exposure. The results demonstrate that protein intensities do not change substantially in response to this stress. Rather, the increased resistance exhibited by the evolved strain may be due in part to increased basal levels of single-stranded binding proteins and a large increase in ribosomal content, possibly allowing for a more robust, induced response during recovery. This experiment provides evidence enabling us to focus on DNA replication, protein production, and ribosome levels for further studies into the mechanism of γ-radiation resistance in E. dermatitidis and other fungi.

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Section: Discussionmentioning

confidence: 99%

Proteomics Reveals Distinct Changes Associated with Increased Gamma Radiation Resistance in the Black Yeast Exophiala dermatitidis

Schultzhaus

Romsdahl

et al. 2020

Genes

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“…cell membranes, proteins, organelles, and melanin) to a greater extent than IR from photons [1,35]. For example, carbon ion (high LET) induced speci c mutations in the S. cerevisiae and the lamentous fungus Neurospora crassa when compared with lower LET irradiation sources (x-rays or γ-rays [36,37]), and irradiation with high or low LET sources produce different cell killing rates based on strain melanization status in C. neoformans [23].…”

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confidence: 99%

The transcriptomic and phenotypic response of the melanized yeast Exophiala dermatitidis to ionizing particle exposure

Schultzhaus

Chen

Shuryak

et al. 2020

Preprint

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Fungi can tolerate extremely high doses of ionizing radiation compared with most other eukaryotes, a phenomenon encompassing both the recovery from acute exposure and the growth of melanized fungi in chronically contaminated environments. This observation has led to the use of fungi in radiobiology studies, with the goal of finding novel resistance mechanisms that could assist fields such as nuclear medicine and space biology. As photonic (x-ray and γ-ray) exposure is the most widely available method for irradiation, little work has been done examining how fungi (other than budding yeast) respond to irradiation by ionizing particles (e.g. protons), although particle irradiation may cause distinct cellular damage, and it is more relevant to environmental exposure profiles. Here, we expand on a previous study of the melanized yeast Exophiala dermatitidis responding to γ-radiation exposure by characterizing the phenotypic and transcriptomic response to irradiation by three different ionizing particles: protons, deuterons, and α-particles. No significant difference in survival was observed between these strains under any condition, suggesting that melanin does not impart protection to acute irradiation to these particles. The transcriptomic response during recovery to particle exposure was similar to that observed after γ-irradiation, with DNA repair and replication genes upregulated, and genes involved in translation and ribosomal biogenesis being heavily repressed, indicating an attenuation of cell growth. However, a comparison of global gene expression showed clear clustering into particle and γ-radiation groups. The response elicited by particle irradiation was more complex. Compared to the γ-associated response, particle irradiation resulted in greater changes in gene expression, a more diverse set of differentially expressed genes, and a significant induction of gene categories such as autophagy and protein catabolism. Additionally, individual particle responses were analyzed and compared, resulting in the discovery of unique expression signatures and individual genes for each particle type that could be used as radio-nuclide discrimination markers. The strong response we observed here at the gene expression level inprovides insights into the unique types of damage that particle irradiation causes to fungal cells, allowing for future dissection of radiation source-specific resistance mechanisms.

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“…The distinction in the biological effects between high and low LET IR sources may be great, as charged particles are known to cause distinct types of DNA damage (e.g., more complex and clustered lesions), and could interact with other cellular structures (e.g., cell membranes, proteins, organelles, and melanin) to a greater extent than IR from photons ( Ward, 1988 ; Hada and Georgakilas, 2008 ). For example, carbon ion (high LET) induced specific mutations in the S. cerevisiae and the filamentous fungus Neurospora crassa when compared with lower LET irradiation sources [X-rays or γ-rays ( Ma et al, 2018 ; Matuo et al, 2019 )], and irradiation with high or low LET sources produce different cell killing rates based on strain melanization status in C. neoformans ( Pacelli et al, 2017a ).…”

Section: Introductionmentioning

confidence: 99%

The Transcriptomic and Phenotypic Response of the Melanized Yeast Exophiala dermatitidis to Ionizing Particle Exposure

et al. 2021

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Fungi can tolerate extremely high doses of ionizing radiation compared with most other eukaryotes, a phenomenon encompassing both the recovery from acute exposure and the growth of melanized fungi in chronically contaminated environments such as nuclear disaster sites. This observation has led to the use of fungi in radiobiology studies, with the goal of finding novel resistance mechanisms. However, it is still not entirely clear what underlies this phenomenon, as genetic studies have not pinpointed unique responses to ionizing radiation in the most resistant fungi. Additionally, little work has been done examining how fungi (other than budding yeast) respond to irradiation by ionizing particles (e.g., protons, α-particles), although particle irradiation may cause distinct cellular damage, and is more relevant for human risks. To address this paucity of data, in this study we have characterized the phenotypic and transcriptomic response of the highly radioresistant yeast Exophiala dermatitidis to irradiation by three separate ionizing radiation sources: protons, deuterons, and α-particles. The experiment was performed with both melanized and non-melanized strains of E. dermatitidis, to determine the effect of this pigment on the response. No significant difference in survival was observed between these strains under any condition, suggesting that melanin does not impart protection to acute irradiation to these particles. The transcriptomic response during recovery to particle exposure was similar to that observed after γ-irradiation, with DNA repair and replication genes upregulated, and genes involved in translation and ribosomal biogenesis being heavily repressed, indicating an attenuation of cell growth. However, a comparison of global gene expression showed clear clustering of particle and γ-radiation groups. The response elicited by particle irradiation was, in total, more complex. Compared to the γ-associated response, particle irradiation resulted in greater changes in gene expression, a more diverse set of differentially expressed genes, and a significant induction of gene categories such as autophagy and protein catabolism. Additionally, analysis of individual particle responses resulted in identification of the first unique expression signatures and individual genes for each particle type that could be used as radionuclide discrimination markers.

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Molecular Analysis of Carbon Ion-Induced Mutations in DNA Repair-Deficient Strains of Saccharomyces cerevisiae

Cited by 7 publications

References 28 publications

Proteomics Reveals Distinct Changes Associated with Increased Gamma Radiation Resistance in the Black Yeast Exophiala dermatitidis

Proteomics Reveals Distinct Changes Associated with Increased Gamma Radiation Resistance in the Black Yeast Exophiala dermatitidis

The transcriptomic and phenotypic response of the melanized yeast Exophiala dermatitidis to ionizing particle exposure

The Transcriptomic and Phenotypic Response of the Melanized Yeast Exophiala dermatitidis to Ionizing Particle Exposure

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