The Diversity and Commonalities of the Radiation-Resistance Mechanisms
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Jin et al. AMB Expr (2019) 9:138 https://doi.org/10.1186/s13568-019-0862-x MINI-REVIEW Open Access The diversity and commonalities of the radiation-resistance mechanisms of Deinococcus and its up-to-date applications Mengmeng Jin1,2, Anqi Xiao3, Liying Zhu3*, Zhidong Zhang4, He Huang5 and Ling Jiang2* Abstract Deinococcus is an extremophilic microorganism found in a wide range of habitats, including hot springs, radiation- contaminated areas, Antarctic soils, deserts, etc., and shows some of the highest levels of resistance to ionizing radia- tion known in nature. The highly efcient radiation-protection mechanisms of Deinococcus depend on a combination of passive and active defense mechanisms, including self-repair of DNA damage (homologous recombination, MMR, ER and ESDSA), efcient cellular damage clearance mechanisms (hydrolysis of damaged proteins, overexpression of repair proteins, etc.), and efective clearance of reactive oxygen species (ROS). Due to these mechanisms, Deinococcus cells are highly resistant to oxidation, radiation and desiccation, which makes them potential chassis cells for wide applications in many felds. This article summarizes the latest research on the radiation-resistance mechanisms of Deinococcus and prospects its biotechnological application potentials. Keywords: Deinococcus, Ionizing radiation, DNA repair, Anti-oxidation Introduction the genes responsible for its radiation-resistance capacity Extremophilic microorganisms have a wide range of and introduced them into other microorganisms through potential applications due to their high resistance to genetic engineering, so as to increase their application extreme environments. Deinococcus is one of the most range. In recent years, D. radiodurans has been investi- radiation-resistant extremophiles in the world, toler- gated as a platform for the bioremediation of contamina- ating up to 15,000 Gy of acute ionizing radiation and tion with radiation or heavy metals, and the treatment 60 Gy/h of chronic radiation (Daly 2006). What’s more, efect was found to be better than using less tolerant its capacity to withstand ionizing radiation is 1000 times microorganisms. that of typical eukaryotes, more than 250 times that of Escherichia. coli, and 3000 times that of humans (Cox Basic properties of Deinococcus and Battista 2005; Makarova et al. 2001). In addition, When D. radiodurans was frst isolated from radiation- the resistance of Deinococcus to drought and hypertonic sterilized corned beef cans by Anderson et al. (Duggan stress is also relatively high. Terefore, Deinococcus radi- et al. 1963) in1956, it was thought to be afliated with odurans has been studied widely since it was discovered, Micrococcus due to morphological similarities. After and has even become a research hotspot in recent years, in-depth research, researchers later classifed it into its both in China and abroad. Its radiation-resistance mech- own family and genus, Deinococcaceae and Deinococcus. anism has been described, and some studies identifed Generally, as shown in Additional fle 1: Table S1, Deino- coccus is a heterotrophic, non-pathogenic, non-motile, *Correspondence: [email protected]; [email protected] non-spore-forming, aerobic tetracoccus (Maisch et al. 2 College of Food Science and Light Industry, Nanjing Tech University, 2012). It develops red or pink, smooth colonies on TGY Nanjing 210009, People’s Republic of China medium (0.5% tryptone, 0.3% yeast extract, 0.1% glucose, 3 College of Chemical and Molecular Engineering, Nanjing Tech University, Nanjing 210009, People’s Republic of China 1.5–2% agar) after 2–3 days of culture at 30 °C. Full list of author information is available at the end of the article © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Jin et al. AMB Expr (2019) 9:138 Page 2 of 12 Te cell envelope of D. radiodurans is thick, which is double-stranded DNA breaks (DSBs). Because of the why most cells stain Gram-positive, but it contains two DNA protection mechanism, the genomes of D. radio- membranes separated by a peptidoglycan layer, which durans are tightly linked and form ring-like nuclei under makes it more similar to typical Gram-negative bacte- IR. Te level of DNA damage in D. radiodurans and E. ria. Some strains of Deinococcus have a cell envelope coli cells induced by IR is similar, but the specifc nucleus- composed of six layers. Te innermost layer is the cell’s like structure in D. radiodurans helps to keep the DNA inner membrane, which is composed of unusual lipids, ends formed by the double-strand break together and including alkylamine chains, followed by a perforated promote their repair. Compared to E. coli cells, which die peptidoglycan cell wall, after which there are unique with 12 double stranded DNA breaks, the DNA repair small compartments. Te fourth layer is the outer plas- system of D. radiodurans is highly efcient and can suc- malemma, the ffth layer is composed of diferent elec- cessfully repair up to 200 double strand breaks without troluminescent regions, and the sixth layer is composed reducing the cell- viability. Daly (Daly 2009) put forward of hexagonal protein subunits (Gerber et al. 2015). Te a view that protein is an important macromolecule sub- whole tetrad is surrounded by a dense carbohydrate stance afected by IR. D. radiodurans accumulates man- shell, which contributes to the biological robustness of ganese complexes (Daly et al. 2004) when exposed to IR, Deinococcus. Deinococcus has a robust and unique struc- which can prevent the production of iron-dependent ture, with cells often forming tetrads (Cox and Battista reactive oxygen species, thereby protecting the activity of 2005, Gerber et al. 2015; Ghosal et al. 2005). It also has enzymes that repair the DNA. Another theory suggested a unique genomic structure, and the condensed genome that IR resistance is predominantly a metabolic phenom- can reduce nucleic acid damage when subjected to exter- enon (Sharma et al. 2017). In this view, IR-resistant cells nal stress (ionizing radiation, UV radiation, oxidation, contain a high cellular content of Mn2+ in high-symmetry drying, mitomycin C, etc.). (H) antioxidant complexes (H-Mn2+) with small metabo- Te analysis and annotation of related gene sequences lites, and the complexes (H-Mn2+) protect the proteome showed an abundant genetic and adaptive diversity of rather than the genome from IR damage. Additionally, a radiation-resistant microorganisms in radiation-contam- cross-kingdom analysis of the diferences in taxonomic inated areas of China, and also showed that there are a classifcation, genome size, and radioresistance between large number of unknown functional gene resources cell types, indicated that small, highly symmetric anti- awaiting discovery in these radiation-contaminated oxidant complexes of manganese ions and metabolites areas, which provides scientifc materials and a theoreti- (H-Mn2+) are responsible for cellular IR resistance, not cal basis for further utilization of these genetic resources. DNA repair systems and antioxidant enzymes (Sharma Te currently known 69 strains of Deinococcus as well as et al. 2017). Te combined action of various mechanisms their characteristics are summarized in Additional fle 1: and evolution of D. radiodurans have enabled the bacte- Table S1. In general, Deinococcus are aerobic, non-motile, ria to resist IR. non-spore forming and non-pathogenic bacteria that grow as red or pink colonies on plates, and mostly stain Efcient repair of DNA damage as Gram-positive in spite of a double membrane. Te Homologous recombination (HR) genus Deinococcus has high resistance to γ-radiation, UV Te multiple copies of the genome of Deinococcus ena- radiation, desiccation and mitomycin C, and colonizes ble efcient repair of double-strand breaks by homolo- a wide range of habitats, including animals and plants, gous recombination. Homologous recombination is the sandy beaches, oceans, the air, deserts, hot springs, high- main way to repair DNA damage. It uses normal and radiation areas, cold polar regions, etc. (Additional fle 1: intact homologous DNA as template to repair damaged Table S1). D. Radiodurans R1 was the frst strain to be DNA, both of which are double-stranded DNA mol- discovered with a resistance to γ-radiation and UV radia- ecules. One of the most important steps in homologous tion, and is a model strain for use in biological research. recombination is the interaction between RecA protein Te complete genome sequence of R1 consists of two and single stranded DNA in areas where double strands chromosomes (2648,638 and 412,348 bp), a megaplas- were broken to produce free 3′ ends by the RecBCD or mid (177,466 bp), and a small plasmid (45,704 bp), and its RecFOR system in bacteria. Because there are no RecB G +C content is 66.6% (White 1999). and RecC proteins in Deinococcus, the RecFOR system plays a major role in DNA terminus processing (Agapov Resistance mechanisms of Deinococcus and Kulbachinskiy 2015). RecN is an adhesin-like chro- As shown in Fig. 1, Deinococcus has a systematic radi- mosome structure maintenance protein and its ATPase ation-resistance mechanism. Ionizing radiation (IR) activity stimulates RecA to invade homologous DNA can produce reactive oxygen species (ROS) and cause strands to form D-loop structures and repair broken Jin et al. AMB Expr (2019) 9:138 Page 3 of 12 Fig. 1 Radiation-resistance mechanisms of Deinococcus double-stranded DNA. Correspondingly, the binding of substitution ability and ssDNA annealing activity. Fur- RecA with DNA can also promote the ATPase activity of thermore, dr1088 is crucial for cell viability, and deleting RecN protein (Uranga et al. 2017). Single-stranded DNA it directly results in growth defects and increased sensi- binding protein (SSB) protects single-stranded DNA tivity to gamma and UV radiation to diferent degrees.