The Experts below are selected from a list of 3174 Experts worldwide ranked by ideXlab platform
Masayori Inouye - One of the best experts on this subject based on the ideXlab platform.
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mazg a nucleoside triphosphate pyrophosphohydrolase interacts with era an essential gtpase in escherichia coli
Journal of Bacteriology, 2002Co-Authors: Junjie Zhang, Masayori InouyeAbstract:Era is an essential GTPase in Escherichia coli, and Era has been implicated in a number of cellular functions. Homologues of Era have been identified in various bacteria and some eukaryotes. Using the era Gene as bait in the yeast two-hybrid system to screen E. coli genomic libraries, we discovered that Era interacts with MazG, a protein of unknown function which is highly conserved among bacteria. The direct interaction between Era and MazG was also confirmed in vitro, being stronger in the presence of GDP than in the presence of GTPgammaS. MazG was characterized as a nucleoside triphosphate pyrophosphohydrolase which can hydrolyze all eight of the canonical ribo- and deoxynucleoside triphosphates to their respective monophosphates and PP(i), with a preference for deoxynucleotides. A mazG deletion strain of E. coli was constructed by replacing the mazG Gene with a kanamycin resistance Gene. Unlike mutT, a Gene for another conserved nucleotide triphosphate pyrophosphohydrolase that functions as a Mutator Gene, the mazG deletion did not result in a Mutator phenotype in E. coli.
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The Gene for Nucleoside Diphosphate Kinase Functions as a Mutator Gene inEscherichia coli
Journal of molecular biology, 1995Co-Authors: Xiaolin Zhang, Niva Almaula, Christopher K. Mathews, Masayori InouyeAbstract:Abstract Nucleoside diphosphate (NDP) kinase is a key enzyme in the control of cellular concentrations of nucleoside triphosphates, and has been shown to play important roles in various cellular activities such as developmental control, signal transduction and metastasis in eukaryotic systems. In this study, the Gene for NDP kinase of Escherichia coli (ndk) was disrupted and surprisingly found to be dispensable without any discernible effects on cell growth or morphology. However, a Mutator phenotype was found in ndk -disruption strains; frequencies of spontaneous mutations to rifampicin resistance and nalidixic acid resistant significantly increased. A higher frequency in reversion mutations was observed with use of an amber mutation in the kanamycin-resistance Gene in an ndk -disruption strain. Imbalance in dNTP pools, in particular a significant increase of the dCTP content was observed, which is likely to result in the higher spontaneous mutation rates. These results suggest that NDP kinase, although not essential, plays an important role in the appropriate balance of intracellular dNTP pools to maintain a high DNA replication fidelity. Strains with ndk − pyk A − pyk F − as well as ndk − scs − were constructed without any discernible effect on cell growth, indicating that there is yet another enzyme(s) catalyzing nucleoside triphosphate synthesis, in addition to NDP kinase, pyruvate kinases and succinyl CoA synthetase.
Kamal F Badr - One of the best experts on this subject based on the ideXlab platform.
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effects of mutant p53 expression on human 15 lipoxygenase promoter activity and murine 12 15 lipoxygenase Gene expression evidence that 15 lipoxygenase is a Mutator Gene
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: Uddhav P Kelavkar, Kamal F BadrAbstract:Human 15-lipoxygenase (h15-LO) is present on chromosome 17p13.3 in close proximity to the tumor-suppressor Gene, p53. 15-LO is implicated in antiinflammation, membrane remodeling, and cancer development/metastasis. The murine BALB/c embryo fibroblast cell line, (10)1val, expresses p53 in mutant (mt) conformation when grown at 39 degrees C and in wild-type conformation when grown at 32 degrees C. Transfection of h15-LO promoter constructs (driving luciferase reporter) into (10)1val cells and into p53-deficient (10)1 cells resulted in a marked increase in h15-LO promoter activity in (10)1val cells at 39 degrees C, but not at 32 degrees C, or as compared with (10)1 cells. Transfection of h15-LO promoter deletion constructs, however, resulted in total loss of activity in both cell types at 32 degrees C and 39 degrees C. Cotransfection of (10)1 cells with h15-LO promoter (driving luciferase reporter) along with increasing levels of a mt p53 expression vector demonstrated dose-dependent capacity of mt p53 to induce 15-LO promoter activity. No effect was observed with wild-type p53. In contrast to h15-LO promoter activity, (10)1val cells had significantly lower levels of endogenous (murine) 12/15-LO (mouse analog of h15-LO) mRNA and protein when grown at 39 degrees C compared with cells grown at 32 degrees C. Our data support the hypothesis that loss of a tumor-suppressor Gene (p53), or "gain-of-function activities" resulting from the expression of its mutant forms, regulates 15-LO promoter activity in man and in mouse, albeit in directionally opposite manners. The studies define a direct link between 15-LO activity and an established tumor-suppressor Gene located in close chromosomal proximity.
Bernard Godelle - One of the best experts on this subject based on the ideXlab platform.
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role of Mutator alleles in adaptive evolution
Nature, 1997Co-Authors: Francois Taddei, Miroslav Radman, J Maynardsmith, Bruno Toupance, Pierrehenri Gouyon, Bernard GodelleAbstract:that the mutation rate has evolved to be as low as possible, limited only by the cost of error-avoidance and error-correction mechanisms. But up to one per cent of natural bacterial isolates are 'Mutator' clones that have high mutation rates 4-6 . We consider here whether high mutation rates might play an important role in adaptive evolution. Models of large, asexual, clonal populations adapting to a new environment show that strong Mutator Genes (such as those that increase mutation rates by 1,000-fold) can accelerate adaptation, even if the Mutator Gene remains at a very low frequency (for example, 10 2 5 ). Less potent Mutators (10 to 100-fold increase) can become fixed in a fraction of finite populations. The parameters of the model have been set to values typical for Escherichia coli cultures, which behave in a manner similar to the model in long-term adaptation experiments 7 . Early models of the evolution of the mutation rate were based on group selection for an optimal compromise between adaptability and adaptedness 2,3 . However, later models, incorporating Mutators and antiMutators (modifiers of the mutation rate) showed that a Mutator can reduce individual fitness while increasing the prob- ability for an adaptive mutation to appear in the population. The prediction of these models was that a minimal mutation rate would be selected in a stable environment (reduction principle 8 ), whereas in an oscillating environment, infinite populations at equilibrium
Uddhav P Kelavkar - One of the best experts on this subject based on the ideXlab platform.
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effects of mutant p53 expression on human 15 lipoxygenase promoter activity and murine 12 15 lipoxygenase Gene expression evidence that 15 lipoxygenase is a Mutator Gene
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: Uddhav P Kelavkar, Kamal F BadrAbstract:Human 15-lipoxygenase (h15-LO) is present on chromosome 17p13.3 in close proximity to the tumor-suppressor Gene, p53. 15-LO is implicated in antiinflammation, membrane remodeling, and cancer development/metastasis. The murine BALB/c embryo fibroblast cell line, (10)1val, expresses p53 in mutant (mt) conformation when grown at 39 degrees C and in wild-type conformation when grown at 32 degrees C. Transfection of h15-LO promoter constructs (driving luciferase reporter) into (10)1val cells and into p53-deficient (10)1 cells resulted in a marked increase in h15-LO promoter activity in (10)1val cells at 39 degrees C, but not at 32 degrees C, or as compared with (10)1 cells. Transfection of h15-LO promoter deletion constructs, however, resulted in total loss of activity in both cell types at 32 degrees C and 39 degrees C. Cotransfection of (10)1 cells with h15-LO promoter (driving luciferase reporter) along with increasing levels of a mt p53 expression vector demonstrated dose-dependent capacity of mt p53 to induce 15-LO promoter activity. No effect was observed with wild-type p53. In contrast to h15-LO promoter activity, (10)1val cells had significantly lower levels of endogenous (murine) 12/15-LO (mouse analog of h15-LO) mRNA and protein when grown at 39 degrees C compared with cells grown at 32 degrees C. Our data support the hypothesis that loss of a tumor-suppressor Gene (p53), or "gain-of-function activities" resulting from the expression of its mutant forms, regulates 15-LO promoter activity in man and in mouse, albeit in directionally opposite manners. The studies define a direct link between 15-LO activity and an established tumor-suppressor Gene located in close chromosomal proximity.
Francois Taddei - One of the best experts on this subject based on the ideXlab platform.
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role of Mutator alleles in adaptive evolution
Nature, 1997Co-Authors: Francois Taddei, Miroslav Radman, J Maynardsmith, Bruno Toupance, Pierrehenri Gouyon, Bernard GodelleAbstract:that the mutation rate has evolved to be as low as possible, limited only by the cost of error-avoidance and error-correction mechanisms. But up to one per cent of natural bacterial isolates are 'Mutator' clones that have high mutation rates 4-6 . We consider here whether high mutation rates might play an important role in adaptive evolution. Models of large, asexual, clonal populations adapting to a new environment show that strong Mutator Genes (such as those that increase mutation rates by 1,000-fold) can accelerate adaptation, even if the Mutator Gene remains at a very low frequency (for example, 10 2 5 ). Less potent Mutators (10 to 100-fold increase) can become fixed in a fraction of finite populations. The parameters of the model have been set to values typical for Escherichia coli cultures, which behave in a manner similar to the model in long-term adaptation experiments 7 . Early models of the evolution of the mutation rate were based on group selection for an optimal compromise between adaptability and adaptedness 2,3 . However, later models, incorporating Mutators and antiMutators (modifiers of the mutation rate) showed that a Mutator can reduce individual fitness while increasing the prob- ability for an adaptive mutation to appear in the population. The prediction of these models was that a minimal mutation rate would be selected in a stable environment (reduction principle 8 ), whereas in an oscillating environment, infinite populations at equilibrium
