Defective excision repair in a mutant of Micrococcus radiodurans hypermutable by some monofunctional alkylating agents

Tempest, Philip R.; Moseley, Bevan

doi:10.1007/bf00268463

Cited by 25 publications

(16 citation statements)

References 30 publications

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“…After the induction of cross-links, DSBs are observed in a neutral sucrose gradient (304). UvrA (4,441,611) and RecA (223,439) are essential for the repair of MMC-induced damage (Fig. 8C), which suggests that, as in E. coli, interstrand cross-links are repaired through the concerted action of NER and homologous recombination (102,163,463).…”

Section: Resistance Of D Radiodurans To Mitomycin Cmentioning

confidence: 92%

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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Section: Resistance Of D Radiodurans To Mitomycin Cmentioning

confidence: 92%

Oxidative Stress Resistance inDeinococcus radiodurans

Slade

Radman

2011

Microbiol Mol Biol Rev

648

639

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“…radiodurans. A large yield of mutants of D. radiodurans can be generated by treating D. radiodurans 302 with the alkylating agent MNNG (25). Strain 302 is approximately 50 times more mutable than the wild-type R1 strain following MNNG treatment because it is a uvrA mutant (i.e., it carries a defect in endonuclease cx).…”

Section: Matermils and Methodsmentioning

confidence: 99%

Novel ionizing radiation-sensitive mutants of Deinococcus radiodurans

et al. 1994

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Two new loci, irrB and irrI, have been identified in Deinococcus radiodurans. Inactivation of either locus results in a partial loss of resistance to ionizing radiation. The magnitude of this loss is locus specific and differentially affected by inactivation of the uvrA gene product. An irrB uvrA double mutant is more sensitive to ionizing radiation than is an irrB mutant. In contrast, the irrI uvrA double mutant and the irrI mutant are equally sensitive to ionizing radiation. The irrB and irrI mutations also reduce D. radiodurans resistance to UV radiation, this effect being most pronounced in uvrA+ backgrounds. Subclones of each gene have been isolated, and the loci have been mapped relative to each other. The irrB and irrI genes are separated by approximately 20 kb of intervening sequence that encodes the uvrA and pol genes.

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“…Both UV endonuclease-a, the product of mtcA, and UV-endonuclease I, the product of uvsCDE, incise UV-irradiated DNA, initiating excision repair of pyrimidine dimers. Neither enzyme appears to be a glycosylase (14,52), and defects in one or both do not affect sensitivity to ionizing radiation (40). Curiously, either activity alone is * Corresponding author.…”

Section: )mentioning

confidence: 99%

Identification, sequencing, and targeted mutagenesis of a DNA polymerase gene required for the extreme radioresistance of Deinococcus radiodurans

et al. 1993

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Deinococcus radiodurans and other species of the same genus share extreme resistance to ionizing radiation and many other agents that damage DNA. Two different DNA damage-sensitive strains generated by chemical mutagenesis were found to be defective in a gene that has extended DNA and protein sequence homology with poL4 of Escherichia coli. Both mutant strains lacked DNA polymerase, as measured in activity gels. Transformation of this gene from wild-type D. radiodurans restored to the mutants both polymerase activity and DNA damage resistance. A technique for targeted insertional mutagenesis in D. radiodurans is presented. This technique was employed to construct a pol mutant isogenic with the wild type (the first example of targeted mutagenesis in this eubacterial family). This insertional mutant lacked DNA polymerase activity and was even more sensitive to DNA damage than the mutants derived by chemical mutagenesis. In the case of ionizing radiation, the survival of the wild type after receiving 1 Mrad was 100%o while survival of the insertional mutant extrapolated to 10-24. These results demonstrate that the gene described here encodes a DNA polymerase and that defects in this pol gene cause a dramatic loss of resistance of D. radiodurans to DNA damage.

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Defective excision repair in a mutant of Micrococcus radiodurans hypermutable by some monofunctional alkylating agents

Cited by 25 publications

References 30 publications

Oxidative Stress Resistance inDeinococcus radiodurans

Oxidative Stress Resistance inDeinococcus radiodurans

Novel ionizing radiation-sensitive mutants of Deinococcus radiodurans

Identification, sequencing, and targeted mutagenesis of a DNA polymerase gene required for the extreme radioresistance of Deinococcus radiodurans

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