The resistances of Micrococcus radiodurans to killing and mutation by agents which damage DNA

Sweet, Diana M.; Moseley, Bevan

doi:10.1016/0027-5107(76)90122-6

Cited by 80 publications

(39 citation statements)

References 23 publications

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“…6A). In contrast, the degrees of resistance of wild-type and complemented mutant strains to UV and mitomycin were undistinguishable and comparable to those previously reported for E. coli (42), taking the low growth rate of M. dichloromethanicum into account (doubling time of about 3.6 h with MeOH at 30°C [ Table 1]). Most notably, the polA mutant from strain DM4 was also sensitive to treatment with DCM (Fig.…”

Section: Resultssupporting

confidence: 86%

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

2000

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Methylobacterium dichloromethanicum DM4 grows with dichloromethane as the unique carbon and energy source by virtue of a single enzyme, dichloromethane dehalogenase-glutathione S-transferase. A mutant of the dichloromethane-degrading strain M. dichloromethanicum DM4, strain DM4-1445, was obtained by mini-Tn5 transposon mutagenesis that was no longer able to grow with dichloromethane. Dichloromethane dehalogenase activity in this mutant was comparable to that of the wild-type strain. The site of mini-Tn5 insertion in this mutant was located in the polA gene encoding DNA polymerase I, an enzyme with a well-known role in DNA repair. DNA polymerase activity was not detected in cell extracts of the polA mutant. Conjugation of a plasmid containing the intact DNA polymerase I gene into the polA mutant restored growth with dichloromethane, indicating that the polA gene defect was responsible for the observed lack of growth of this mutant with dichloromethane. Viability of the DM4-1445 mutant was strongly reduced upon exposure to both UV light and dichloromethane. The polA -lacZ transcriptional fusion resulting from mini-Tn5 insertion was constitutively expressed at high levels and induced about twofold after addition of 10 mM dichloromethane. Taken together, these data indicate that DNA polymerase I is essential for growth of M. dichloromethanicum DM4 with dichloromethane and further suggest an important role of the DNA repair machinery in the degradation of halogenated, DNA-alkylating compounds by bacteria.Dichloromethane (DCM) is an organic solvent produced industrially in large amounts for a wide range of technical applications (Halogen Solvents Industry Alliance [http://www .hsia.org/white_papers/methchlor.htm]). Its low boiling point and high solubility in water make it a frequently encountered environmental contaminant (36,46). The toxicity of DCM to mammals continues to be investigated intensively (9,14,21,40,45), but its causes are not yet fully characterized at the molecular level. Many specialized aerobic methylotrophic bacteria have been isolated from soil and groundwater environments contaminated with DCM for their ability to grow with DCM as the sole source of carbon and energy (49). Such bacteria rely on a single enzyme, DCM dehalogenase, for this purpose. DCM dehalogenase, which can make up to 20% of the soluble protein during bacterial growth with DCM, was purified and shown to catalyze the glutathione-dependent transformation of DCM to formaldehyde, used in both biomass and energy production, and to two molecules of hydrochloric acid (31). The corresponding gene dcmA was cloned (33) from Methylobacterium dichloromethanicum DM4 (15) (formerly Methylobacterium sp. strain DM4), Methylophilus sp. strain DM11 (3), and, more recently, from several other DCM-degrading strains (49, 50). Sequence analysis indicates that DCM dehalogenases belong to the glutathione S-transferase (GST) enzyme family (27,47). DCM dehalogenases were the first bacterial GSTs to be characterized, but it is becoming clear that the genom...

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Section: Resultssupporting

confidence: 86%

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

2000

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“…Furthermore, survivors of extreme ionizing radiation, UV, or bulky chemical-adduct exposures do not show any mutagenesis greater than that occurring after a single round of normal replication (197,198). On the other hand, D. radiodurans is mutable by N-methyl-NЈ-nitro-N-nitrosoguanidine and other agents that can cause mispairing of bases during replication (197,198). Of the many forms of damage imposed on DNA by ionizing radiation, DSBs are considered the most lethal due to the inherent difficulty in their repair, since no single-strand template for accurate repair remains in the double helix (117).…”

Section: Dna Damage Resistancementioning

confidence: 98%

“…Compared to other organisms, the D. radiodurans DNA sustains the expected amount of damage in vivo at high irradiation doses, on the order of 150 to 200 double-stranded DNA breaks (DSBs) at 1.5 megarads per haploid chromosome under aerobic irradiation conditions, all of which are mended within hours following irradiation (53,107,123), nor is its DNA less susceptible than that of E. coli to UV in vivo (183). Furthermore, survivors of extreme ionizing radiation, UV, or bulky chemical-adduct exposures do not show any mutagenesis greater than that occurring after a single round of normal replication (197,198). On the other hand, D. radiodurans is mutable by N-methyl-NЈ-nitro-N-nitrosoguanidine and other agents that can cause mispairing of bases during replication (197,198).…”

Section: Dna Damage Resistancementioning

confidence: 99%

Genome of the Extremely Radiation-Resistant Bacterium Deinococcus radiodurans Viewed from the Perspective of Comparative Genomics

Makarova

Aravind

Wolf

et al. 2001

Microbiol Mol Biol Rev

646

612

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The bacterium Deinococcus radiodurans shows remarkable resistance to a range of damage caused by ionizing radiation, desiccation, UV radiation, oxidizing agents, and electrophilic mutagens. D. radiodurans is best known for its extreme resistance to ionizing radiation; not only can it grow continuously in the presence of chronic radiation (6 kilorads/h), but also it can survive acute exposures to gamma radiation exceeding 1,500 kilorads without dying or undergoing induced mutation. These characteristics were the impetus for sequencing the genome of D. radiodurans and the ongoing development of its use for bioremediation of radioactive wastes. Although it is known that these multiple resistance phenotypes stem from efficient DNA repair processes, the mechanisms underlying these extraordinary repair capabilities remain poorly understood. In this work we present an extensive comparative sequence analysis of the Deinococcus genome. Deinococcus is the first representative with a completely sequenced genome from a distinct bacterial lineage of extremophiles, the Thermus-Deinococcus group. Phylogenetic tree analysis, combined with the identification of several synapomorphies between Thermus and Deinococcus, supports the hypothesis that it is an ancient group with no clear affinities to any of the other known bacterial lineages. Distinctive features of the Deinococcus genome as well as features shared with other free-living bacteria were revealed by comparison of its proteome to the collection of clusters of orthologous groups of proteins. Analysis of paralogs in Deinococcus has revealed several unique protein families. In addition, specific expansions of several other families including phosphatases, proteases, acyltransferases, and Nudix family pyrophosphohydrolases were detected. Genes that potentially affect DNA repair and recombination and stress responses were investigated in detail. Some proteins appear to have been horizontally transferred from eukaryotes and are not present in other bacteria. For example, three proteins homologous to plant desiccation resistance proteins were identified, and these are particularly interesting because of the correlation between desiccation and radiation resistance. Compared to other bacteria, the D. radiodurans genome is enriched in repetitive sequences, namely, IS-like transposons and small intergenic repeats. In combination, these observations suggest that several different biological mechanisms contribute to the multiple DNA repair-dependent phenotypes of this organism

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“…A dose of 6 kGy induces approximately 200 DSBs (79), over 3,000 SSBs (65,79), and many more sites of base damage per D. radiodurans genome (236). D. radiodurans survives 5 kGy of ionizing radiation without lethality or mutagenesis (135,161,597) (Fig. 3A).…”

Section: Ionizing Radiation Resistance Of D Radioduransmentioning

confidence: 99%

Oxidative Stress Resistance inDeinococcus radiodurans

Slade

Radman

2011

Microbiol Mol Biol Rev

648

639

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SUMMARY Deinococcus radiodurans is a robust bacterium best known for its capacity to repair massive DNA damage efficiently and accurately. It is extremely resistant to many DNA-damaging agents, including ionizing radiation and UV radiation (100 to 295 nm), desiccation, and mitomycin C, which induce oxidative damage not only to DNA but also to all cellular macromolecules via the production of reactive oxygen species. The extreme resilience of D. radiodurans to oxidative stress is imparted synergistically by an efficient protection of proteins against oxidative stress and an efficient DNA repair mechanism, enhanced by functional redundancies in both systems. D. radiodurans assets for the prevention of and recovery from oxidative stress are extensively reviewed here. Radiation- and desiccation-resistant bacteria such as D. radiodurans have substantially lower protein oxidation levels than do sensitive bacteria but have similar yields of DNA double-strand breaks. These findings challenge the concept of DNA as the primary target of radiation toxicity while advancing protein damage, and the protection of proteins against oxidative damage, as a new paradigm of radiation toxicity and survival. The protection of DNA repair and other proteins against oxidative damage is imparted by enzymatic and nonenzymatic antioxidant defense systems dominated by divalent manganese complexes. Given that oxidative stress caused by the accumulation of reactive oxygen species is associated with aging and cancer, a comprehensive outlook on D. radiodurans strategies of combating oxidative stress may open new avenues for antiaging and anticancer treatments. The study of the antioxidation protection in D. radiodurans is therefore of considerable potential interest for medicine and public health.

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The resistances of Micrococcus radiodurans to killing and mutation by agents which damage DNA

Cited by 80 publications

References 23 publications

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

Genome of the Extremely Radiation-Resistant Bacterium Deinococcus radiodurans Viewed from the Perspective of Comparative Genomics

Oxidative Stress Resistance inDeinococcus radiodurans

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