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At least 19 recordsLinked to original sources
PubMed1976

Misrepair of overlapping daughter strand gaps as a possible mechanism for UV induced mutagenesis in UVR strains of Escherichia coli: a general model for induced mutagenesis by misrepair (SOS repair) of closely spaced DNA lesions.

It has been previously reported that an inducible form of post-replication repair appeared to be required for UV induced mutagenesis in a uvrA strain of Escherichia coli. It is shown here that the numbers of daughter strand gaps requiring inducible repair were similar to the numbers calculated to be overlapping one another in opposite daughter chromosomes. An estimation of survival with no repair of these gaps resembled the survival predicted with no mutagenesis. It is the thus proposed that inducible post-replication repair causes mutagenesis by the repair of overlapping daughter strand gaps. A general model for induced mutagenesis is presented. It is proposed that (a) some DNA lesions introduced by any DNA damaging agent may be close enough to interfere with constitutive repair replication of each other, (b) these lesions induce a repair system (SOS repair) which involves the recA+ lexA+ and polC+ genes (c) repair and concomitant mutagenesis occurs during repair replication by the insertion of mismatched bases opposite the noncoding DNA lesions.

Cell Survival↗
PubMed1976

The dependence of HNO2 mutagenesis in phage T4 on ligase and the lack of dependence of 2AP mutagenesis on repair functions.

A temperature sensitive ligase allele of phage T4 reduced or eliminated HNO2 induced reversion of am mutants. Since at the temperatures used, the ligase mutant is defective in the repair of some types of lethal lesions (i.e., UV, MMS and EMS induced lesions) these results indicate that HNO2 mutagenesis may occur through a ligase dependent repair pathway. In contrast, 2AP induced mutation was not inhibited by mutants defective in the gene 30 ligase or in genes 32, 39, 41, 42, 44, 45, 46, 47, 49, 52, 56, 58-61 and v. This indicates that 2AP mutagenesis probably does not depend on a repair pathway in phage T4.

2-Aminopurine↗
PubMed1976

Mutagenesis in bacteriophage T7. I. Chemically induced mutagenesis.

The mutagenesis in phage T7 after MMS-, HNO2-, hydroxylamine-, 5-BUdR-, and 2-AP-treatment in relation to host controlled functions is investigated. There was no dependence of the induction of mutations on the character of the host strains (rec, hcr). A back mutation system (amber system) and a forward mutation system (host range system) have been used. Substances which cause mainly transitions from GC to AT do not lead or only rarely lead to reversions of the amber system; but chemicals producing transitions from AT to GC do so.

2-Aminopurine↗
PubMed1976

Mutagenesis in bacteriophage T7. II. UV induced mutagenesis.

UV induced mutagenesis of bacteriophage T7 was investigated by using a forward mutation system (host range system) and a back mutation system (amber system). The results indicate a dependence of mutation of T7 after UV irradiation only on the rec gene controlled functions of the bacterial host. The functions controlled by pol and uvr genes have no influence. Among other types of mutations UV irradiation leads to transitions from AT to GC.

Caffeine↗
PubMed1978

Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. I. Isolation of uvm mutants and their phenotypical characterization in DNA repair and mutagenesis.

Selection for defective reversion induction, after UV treatment of E. coli K 12, yielded uvm mutants. These mutants exhibited highly reduced or no UV mutability for all loci tested although they were moderately and normally mutable by X-rays and EMS, respectively. Uvm mutations confer only a slight sensitivity to killing by UV and X-rays and no clear sensitivity to the lethal effect of HN2, EMS or MMS. Growth and viability of untreated uvm cells were normal. The properties of uvm mutants are discussed in relation to those of other relevant mutant types and to some actual problems of induced mutagenesis.

DNA Repair↗
PubMed1978

Bromodeoxyuridine mutagenesis in mammalian cells: mutagenesis is independent of the amount of bromouracil in DNA.

Studies were undertaken to determine how a line of mutant Syrian hamster melanoma cells (HAB-2E) that displays unlimited growth potential when all of the thymine residues in nuclear DNA are replaced by bromouracil (BrUra) could avoid the deleterious effects of bromodeoxyuridine (BrdUrd) mutagenicity. It was found that BrdUrd could be mutagenic to these cells. However, there was a nonlinear relationship between mutagenicity and the amount of BrUra in the DNA of the HAB-2E cells. With these cells, mutagenicity apparently is determined by the concentration of BrdUrd to which the cells are exposed rather than the amount of BrUra in DNA. These results were obtained with both the induction of ouabain resistance and thioguanine resistance as markers for mutagenesis. The dependence of BrdUrd mutagenicity on BrdUrd concentration was also observed for the parental melanoma cells.

Bromodeoxyuridine↗
PubMed1979

Genetic analysis of gamma-ray mutagenesis in yeast. II. Allele-specific control of mutagenesis.

We find that partially different sets of gene functions are required for the production of different kinds of mutations induced by 60Co gamma rays in Saccharomyces cerevisiae. This observation is very similar to others made previously with respect to UV mutagenesis (LAWRENCE and CHRISTENSEN 1978a,b, 1979) and confirms the conclusion that such distinctive patterns of genetic control reflect properties of the test alleles and their genetic locations, rather than the kinds of lesions required to revert them. The data also support the model of mutagenic repair outlined in the first paper of this series (McKee and LAWRENCE 1979), in which partially different sets of gene functions are required for the production of different kinds of mutations, the formation of mutations at different genetic sites and the induction of mutations by different mutagens.

Alleles↗
PubMed1978

Mechanisms of bacterial mutagenesis and properties of mutagenesis tester strains.

Bacterial tester strains are available which can detect base pair substitution, frameshift and deletion mutations. I consider possible mechanisms for these types of event. I describe the four main types of DNA repair process operating in Escherichia coli and Salmonella typhimurium and how they may influence mutation: Means of modifying repair processes to increase the sensitivity of tester strains are discussed. The properties of some current strains are briefly described. I comment adversely on forward mutation systems and discuss aspects of the strategy and methodology of mutagenicity testing with bacteria.

DNA Repair↗
PubMed1979

[Chemotherapy and mutagenesis. A study of chromosome aberrations as a test for mutagenesis after the use of cyclophosphamide, methotrexate and cytosine arabinoside].

Determination of chromosomal aberration in the lymphocyte cell culture of the peripheral blood in 50 children with malignant and nonmalignant diseases was the test applied in the investigation of the adverse effects of the cytostatic therapy on the human genome. The study included the cytostatic drugs cyclophosphamide, methotrexat and cytosine arabinoside which are used in the treatment for the autoimmune diseases, in organ and bone marrow transplantations and in malignant diseases. It was confirmed that these cytostatics could be the cause of considerable structural aberrations in chromosomes, particularly so when high dosages and long application are involved. Therefore it is understandable that these drugs as mutagens can be the cause of the secondary cancer in patients treated with cytostatic therapy and also of the congenital malformations in children by mothers treated with these medications.

Child↗
PubMed1976

[UV-mutagenesis in Bacillus subtilis. VI. Mutagenesis under conditions of experimental delay of post-radiation DNA replication].

To test a suggestion that mutation frequency decline (MFD) in UV-irradiated bacteria starved by nitrogen sources is caused by long delay of the first postradiation cycle of DNA replication, we used a strain 1201-05 of Bacillus subtilis 168 (ade6 met5tsdnaC) which does not synthesize DNA at 42 degrees C. In a suspension of UV-irradiated cells of this strain which is incubated at 42 degrees in liquid deprived by nitrogen sources, a decrease of frequencies of Ade+ and Met+ revertants is observed. This shows that the mechanism responsible for MFD normally operates at higher temperature. Such a level of decline is not observed in a suspension incubated in nutritional medium when the DNA replication is blocked by non-permissive temperature for the same period as in starved cells. On the basis of these facts it is concluded that MFD in suspension of bacteria starved by nitrogen sources can not be caused only by delay of postradiation replication of DNA.

Bacillus subtilis↗
PubMed2026

Innovations in microbial physical mutagenesis for food fermentation: An overview from traditional to emerging technologies.

Microbial strains serve as an important factor affecting fermentation efficiency and product quality. To obtain superior strains, mutation breeding is a classic strategy. Compared to chemical mutagenesis, physical mutagenesis directly induces genomic changes, providing notable advantages such as the elimination of chemical residues and environmental sustainability, hence rendering it a favored method for enhancing food-grade microorganisms. Conventional physical mutagenesis mostly depends on UV, rays, high pressure, or space radiation. As physical technologies advance, emerging methods such as ion implantation, plasma, microwave, ultrasound, and pulsed light are widely utilized for genetic modification. Mutagenesis technologies are progressively transitioning from single-effect to multi-effect synergy. Recent evaluations indicate that emerging technologies can enhance microbial mutation efficiency at the application level relative to established technologies. Nonetheless, the systematic clarification and comparative analysis at the mechanistic level remain inadequate, hindering intuitive comprehension of the qualities and distinctions across techniques. Furthermore, physical mutagenesis encounters several significant obstacles, such as cellular damage, limited rates of advantageous mutations, and laborious screening processes. This review carefully elucidates the mechanisms and properties of physical mutagenesis technology and delineates the distinctions among approaches through comparative analysis. Simultaneously, solutions for optimizing mutagenesis are presented to tackle the principal challenges mentioned above. This review aims to offer a theoretical foundation and practical guidance for the enhanced application of physical mutagenesis technologies in microbial breeding.

Mutagenesis↗
PubMed1977

Mutagenesis of lambda phage: 5-bromouracil and hydroxylamine.

Mutagenesis by 5-bromouracil of lambda phage to clear plaque formers does not depend on the recA function of the host E. coli cell or on the red function of the phage. Pretreatment of the host cells with ultraviolet light does not affect bromouracil mutagenesis of the adsorbed phage. Mutagenesis by hydroxlamine to clear plaque formers takes place at a high level in recA- host cells, and is not changed by preirradiation of of rec+ (wild type) hosts with ultraviolet light. Thus, bromouracil and hydroxylamine appear to mutate lambda phage by a process which differs from that responsible for ultraviolet mutagenesis. Two characteristics of bromouracil mutagenesis--the nonlinear dependence of the number of mutants on bromouracil incorporation, and a high frequency of heterozygotes--fit in with Rydberg's (1977) picture of bromouracil mutagenesis as a consequence of base mispairing, with mismatch repair removing the mutations at low incorporation of the analog.

Bromouracil↗
PubMed1978

Pathways of mutagenesis and repair in Escherichia coli exposed to low levels of simple alkylating agents.

Mutagenesis by simple alkylating agents is thought to occur by either a lexA+-dependent process called error-prone repair or a lex-independent process often attributed to mispairing during replication. We show here that error-prone repair is responsible for the majority of mutants formed after a large dose of alkylating agent, but it is unlikely that it contributes significantly to mutagenesis during exposure to low concentrations of these chemicals. The mutagenicity of these low doses of alkylating agent is reduced by a repair system constitutively present in lexA+ cells but absent in lexA mutants. This system reduces mutagenesis until a second error-free system, called the adaptive responses, can be induced [P. Jeggo, M. Defais, L. Samson, and P. Schendel, Mol. Gen. Genet, 157:1-9, 1977; L. Samson and J. Cairns, Nature (London) 267:281-283, 1977]. The adaptive response is capable of dealing with a much larger amount of alkylation damage than the constitutive system and, when induced, appears to be able to reduce mutagenesis by both decreasing the number of sites available for mutagenesis and delaying the induction of error-prone repair enzymes. Finally, we discuss a model of chemically induced mutagenesis based on these findings which maintains that the observed mutation frequency is dependent on a "race" between these two error-free systems and the two mutagenic pathways.

Alkylating Agents↗
PubMed2026

Intratumoral Mycobacterium abscessus promotes cytidine deaminase mutagenesis in non-small cell lung cancer.

The intratumoral microbiota is increasingly recognized as an active component of the tumor microenvironment, yet whether it directly drives tumor mutagenesis remains unclear. Here, integrated multi-omics analysis of human non-small cell lung cancer (NSCLC) identifies Mycobacterium abscessus as a microbial determinant of APOBEC3A-associated mutagenesis. Mechanistically, the bacterial effector nucleoside diphosphate kinase (NDK) directly targets the host transcription factor IRF3 and installs a non-canonical 1-phosphohistidine modification at H263, thereby amplifying type I interferon signaling and sustaining APOBEC3A expression. This inter-kingdom phosphotransfer event links intratumoral microbial colonization to an endogenous mutational process that promotes genomic diversification. Genetic inactivation of NDK, or pharmacologic elimination using an engineered NDK-PROTAC, suppresses APOBEC3A activation and attenuates microbe driven mutagenesis. Together, these findings establish a direct microbial effector mechanism that promotes APOBEC3A-associated mutagenesis and provide a therapeutic framework to intercept microbiome driven mutagenesis in NSCLC.

Humans↗
PubMed1979

Bromodeoxyuridine mutagenesis in mammalian cells is stimulated by purine deoxyribonucleosides.

The effects of purine deoxyribonucleosides on bromodeoxyurdine (BrdU) mutagenesis in Syrian hamster melanoma cells were determined. Both deoxyguanosine (dG) and deoxyadenosine (dA) were found to stimulate mutagenesis without changing the amount of BrdU in DNA. In addition, the stimulation of mutagenesis by dG and dA was suppressed by the addition of deoxycytidine (dC). These results suggest that BrdU mutagenesis involves the perturbation of dC metabolism, which perturbation is enhanced by dGTP and dATP. The mutagenic activity of dG in the absence of BrdU was tested, as was that of thymidine (dT), which we had shown previously to stimulate BrdU mutageneis. With dG alone, no increase above the spontaneous mutation frequency was detected. However, at extremely high concentration, dT in the absence of BrdU was slightly mutagenic, and the mutagenesis by dT was enhanced by dG and suppressed by dC.

Animals↗
PubMed1978

Antimutagenic effects of caffeine during nitrosoguanidine-induced mutagenesis of Salmonella typhimurium cells and phages.

The effect of caffeine on nitrosoguanidine-induced mutagenesis of Salmonella typhimurium and its P22 and L phages was studied. The detected mutations included phage "clear" mutations, reversions of phage "amber" mutation, and prototrophic reversions of the his- auxotroph of Salmonella typhimurium. Neither the recA mutation of the host nor the erf mutation of the phage genome were found to affect the nitrosoguanidine-induced mutagenesis of the phage during vegetative growth. Beginning with a concentration of 0.2 mg/ml, caffeine decreased the frequency of mutants by 30--60%, attaining a maximum effect at 1.5 mg/ml and retaining this effect even at higher concentrations. A similar antimutagenic effect was observed with the mutagenesis of the host cells. The nitrosoguanidine-induced mutagenesis does not seem to be related to the function of the recA cell gene or the erf phage gene. The mechanism of mutagenesis by nitrosoguanidine probably has two components, one of them caffeine sensitive, the other caffeine-resistant.

Caffeine↗
PubMed1976

Effect of excision repair on azide-induced mutagenesis.

Azide mutagenesis was investigated in Salmonella typhimurium and Escherichia coli. Azide was highly effective in inducing his+ revertants in excision-repair deficient (uvrB) derivatives of S. typhimurium hisG46 and in inducing high frequencies of 5-fluorouracil resistant mutants in excision-repair deficient (uvrA) derivatives of E. coli B/r WP2. In excision-repair plus strains, azide was only a marginal or ineffective mutagen, demonstrating that the bacterial excision-repair system could repair nearly all azide-induced damage. This observation suggests that the initial azide-induced lesion causes a major DNA helix distortion recognizable by the excision-repair endonucleases. The presence of recombination deficient (recB or recC) genes in combination with uvrA increased E. coli sensitivity to azide killing, but depressed azide mutagenicity. These results are similar to those reported for UV-induced mutagenesis with the E. coli strains and suggest that post-replication repair might be the error-prone step in the repair process. Azide mutagenesis specificity is, however, unique and different from UV, as demonstrated by inability of azide to revert the ochre try locus in E. coli WP2s. These results show that the initial azide-induced DNA damage is highly specific but different from UV-induced DNA damage. Metabolic inhibitors, similar in action to azide, did not induce mutations in S. typhimurium strain TA1530, a strain highly susceptible to azide mutagenesis, thus ruling out the possibility that azide mutagenesis was due to peroxide accumulation. A mechanism based on in vivo activation of azide to the actual mutagen is proposed.

Azides↗