Deinococcus radiodurans is extraordinarily resistant to DNA damage, because of its unusually efficient DNA repair processes. The mtcA ؉ and mtcB ؉ genes of D. radiodurans, both implicated in excision repair, have been cloned and sequenced, showing that they are a single gene, highly homologous to the uvrA ؉ genes of other bacteria. The Escherichia coli uvrA ؉ gene was expressed in mtcA and mtcB strains, and it produced a high degree of complementation of the repair defect in these strains, suggesting that the UvrA protein of D. radiodurans is necessary but not sufficient to produce extreme DNA damage resistance. Upstream of the uvrA ؉ gene are two large open reading frames, both of which are directionally divergent from the uvrA ؉ gene. Evidence is presented that the proximal of these open reading frames may be irrB ؉ .Deinococcus (formerly Micrococcus) radiodurans and other members of the same genus share extraordinary resistance to the lethal and mutagenic effects of UV-and ionizing radiation and chemical agents that form bulky adducts and cross-links in DNA (27,(47)(48)(49). While it is known that this extreme resistance to DNA damage is due to exceedingly efficient DNA repair, the precise repair mechanisms involved are poorly understood (33). Two mitomycin (MM)-sensitive strains of D. radiodurans, 302 and 262, carrying mutations that were in genes designated mtcA and mtcB, respectively, were obtained by chemical mutagenesis using N-methyl-NЈ-nitro-N-nitrosoguanidine (MNNG) (34). These strains, however, were not sensitive to UV (254 nm) but were sensitive to bulky alkylating agents. The mtcA strain was further mutagenized, yielding UVsensitive isolates designated as being doubly defective in mtcA and one of the following loci : uvsC, uvsD, and uvsE (35). It was proposed that in D. radiodurans there are two endonucleases that recognize pyrimidine dimers in DNA, one encoded by mtcA and mtcB (UV endonuclease-␣) and the other encoded by uvsC, uvsD, and uvsE (UV endonuclease-␤) (2,17,35); that either of these two endonucleases is independently sufficient to endow D. radiodurans with wild-type resistance to UV; and that both had to be inactivated to obtain a UV-sensitive, excisionless phenotype. While UV endonuclease-␣ has not been detected in vitro, UV endonuclease-␤ has been identified as a 36,000-Da nuclease absent in uvsC-, uvsD-, or uvsE-mutant extracts. It has no known substrate other than pyrimidine dimers and incises as an endonuclease rather than as a glycosylase (15,17). On the other hand, it is believed that UV endonuclease-␣ (mtcA ϩ mtcB ϩ ) not only recognizes UV-induced bipyrimidine damage but also recognizes bulky chemical adducts and interstrand cross-links (2,17,32,35).In this communication, we report that the mtcA ϩ and mtcB ϩ genes are a single gene that is highly homologous to the uvrA ϩ genes of other bacteria and that its gene product is functionally similar to the UvrA protein of Escherichia coli.(A preliminary account of this work was given in a review article [32].) MATERIALS AND METHODSBac...

The sustained activity of Albugranin in mice and monkeys demonstrated in these studies suggests that this agent could be given less frequently than Filgrastim to achieve similar therapeutic effects in patients.

Interferon (IFN) can either prevent or exacerbate the pathogenic effects of the diabetogenic variant of encephalomyocarditis (EMC-D) virus. The effect seen is dependent upon the mouse strain and the time of IFN administration. For example, IFN-alpha beta protects SWR/J but not ICR Swiss male mice against the diabetogenic effects of the virus. Administration of either IFN-alpha beta or the IFN-inducer poly(I):poly(C) 4 days post infection, results in an exacerbation of the infection in ICR Swiss and C57BL/6 male mice. Studies have been initiated to investigate the role of the IFN system in the pathogenesis of this virus infection. In this study IFNs or poly(I):poly(C) were administered to several mouse strains at 24 h before or 4 days after infection with EMC-D virus. The results of such treatment ranged from complete protection of the animals from the diabetogenic effects of the virus to exacerbation of the infection as reflected by the virus content in selected organs. The effect was dependent upon the mouse strain, the type of IFN, and the time of its administration in relation to virus infection.

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