Schultzhaus Zachary, Chen Amy, Shuryak Igor, Wang Zheng
Center for Biomolecular Science and Engineering, United States Naval Research Laboratory, Washington, DC, United States.
Virginia Tech Carilion School of Medicine, Roanoke, VA, United States.
Front Microbiol. 2021 Jan 12;11:609996. doi: 10.3389/fmicb.2020.609996. eCollection 2020.
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 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 , 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.
与大多数其他真核生物相比，真菌能够耐受极高剂量的电离辐射，这一现象既包括从急性辐射暴露中恢复，也包括黑化真菌在核灾难现场等长期受污染环境中的生长。这一观察结果促使人们在放射生物学研究中使用真菌，目的是寻找新的抗性机制。然而，目前仍不完全清楚这一现象的背后原因，因为遗传学研究尚未确定最具抗性的真菌对电离辐射的独特反应。此外，关于真菌（除芽殖酵母外）如何响应电离粒子（如质子、α粒子）辐射的研究很少，尽管粒子辐射可能会导致不同的细胞损伤，并且与人类风险更相关。为了解决这一数据匮乏的问题，在本研究中，我们对高度耐辐射酵母对三种不同电离辐射源（质子、氘核和α粒子）照射的表型和转录组反应进行了表征。实验使用了黑化和非黑化的菌株，以确定这种色素对反应的影响。在任何条件下，这些菌株之间均未观察到存活率的显著差异，这表明黑色素对这些粒子的急性辐射没有保护作用。恢复粒子暴露期间的转录组反应与γ辐射后观察到的反应相似，DNA修复和复制基因上调，而参与翻译和核糖体生物合成的基因受到严重抑制，表明细胞生长减弱。然而，整体基因表达的比较显示粒子和γ辐射组明显聚类。粒子辐射引发的反应总体上更为复杂。与γ相关反应相比，粒子辐射导致基因表达变化更大、差异表达基因集更多样化，以及自噬和蛋白质分解代谢等基因类别显著诱导。此外，对单个粒子反应的分析导致鉴定出每种粒子类型的首个独特表达特征和单个基因，这些可作为放射性核素鉴别标记。
