| 1. |
- Gummesson, Bertil, 1977, et al.
(författare)
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Increased RNA polymerase availability directs resources towards growth at the expense of maintenance. : RNAP overproduction
- 2009
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Ingår i: The EMBO journal. - : Wiley. - 1460-2075 .- 0261-4189. ; 28:15, s. 2209-2219
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Tidskriftsartikel (refereegranskat)abstract
- Nutritionally induced changes in RNA polymerase availability have been hypothesized to be an evolutionary primeval mechanism for regulation of gene expression and several contrasting models have been proposed to explain how such 'passive' regulation might occur. We demonstrate here that ectopically elevating Escherichia coli RNA polymerase (Esigma(70)) levels causes an increased expression and promoter occupancy of ribosomal genes at the expense of stress-defense genes and amino acid biosynthetic operons. Phenotypically, cells overproducing Esigma(70) favours growth and reproduction at the expense of motility and damage protection; a response reminiscent of cells with no or diminished levels of the alarmone guanosine tetraphosphate (ppGpp). Consistently, we show that cells lacking ppGpp displayed markedly elevated levels of free Esigma(70) compared with wild-type cells and that the repression of ribosomal RNA expression and reduced growth rate of mutants with constitutively elevated levels of ppGpp can be suppressed by overproducing Esigma(70). We conclude that ppGpp modulates the levels of free Esigma(70) and that this is an integral part of the alarmone's means of regulating a trade-off between growth and maintenance.
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| 2. |
- Jansson, Kristina, 1969, et al.
(författare)
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The tumor suppressor homolog in fission yeast, myh1+, displays a strong interaction with the checkpoint gene rad1
- 2008
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Ingår i: Mutation Research. - : Elsevier BV. ; 644, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- The DNA glycosylase MutY is strongly conserved in evolution, and homologs are found in most eukaryotes and prokaryotes examined. This protein is implicated in repair of oxidative DNA damage, in particular adenine mispaired opposite 7,8-dihydro-8-oxoguanine. Previous investigations in Escherichia coli, fission yeast, and mammalian cells show an association of mutations in MutY homologs with a mutator phenotype and carcinogenesis. Eukaryotic MutY homologs physically associate with several proteins with a role in replication, DNA repair, and checkpoint signaling, specifically the trimeric 9-1-1 complex. In a genetic investigation of the fission yeast MutY homolog, myh1+, we show that the myh1 mutation confers a moderately increased UV sensitivity alone and in combination with mutations in several DNA repair genes. The myh1 rad1, and to a lesser degree myh1 rad9, double mutants display a synthetic interaction resulting in enhanced sensitivity to DNA damaging agents and hydroxyurea. UV irradiation of myh1 rad1 double mutants results in severe chromosome segregation defects and visible DNA fragmentation, and a failure to activate the checkpoint. Additionally, myh1 rad1 double mutants exhibit morphological defects in the absence of DNA damaging agents.We also found a moderate suppression of the slow growth and UV sensitivity of rhp51 mutants by the myh1 mutation. Our results implicate fission yeast Myh1 in repair of a wider range of DNA damage than previously thought, and functionally link it to the checkpoint pathway.
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| 3. |
- Magnusson, Lisa U., 1975, et al.
(författare)
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Identical, independent, and opposing roles of ppGpp and DksA in Escherichia coli.
- 2007
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Ingår i: Journal of bacteriology. - 0021-9193. ; 189:14, s. 5193-202
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Tidskriftsartikel (refereegranskat)abstract
- The recent discovery that the protein DksA acts as a coregulator of genes controlled by ppGpp led us to investigate the similarities and differences between the relaxed phenotype of a ppGpp-deficient mutant and the phenotype of a strain lacking DksA. We demonstrate that the absence of DksA and ppGpp has similar effects on many of the observed phenotypes but that DksA and ppGpp also have independent and sometimes opposing roles in the cell. Specifically, we show that overexpression of DksA can compensate for the loss of ppGpp with respect to transcription of the promoters P(uspA), P(livJ), and P(rrnBP1) as well as amino acid auxotrophy, cell-cell aggregation, motility, filamentation, and stationary phase morphology, suggesting that DksA can function without ppGpp in regulating gene expression. In addition, ppGpp and DksA have opposing effects on adhesion. In the course of our analysis, we also discovered new features of the relaxed mutant, namely, defects in cell-cell aggregation and motility.
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| 4. |
- Magnusson, Lisa U., 1975, et al.
(författare)
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ppGpp: a global regulator in Escherichia coli
- 2005
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Ingår i: TRENDS in Microbiology. - : Elsevier BV. - 0966-842X. ; 13:5, s. 236-42
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Tidskriftsartikel (refereegranskat)abstract
- The small nucleotide ppGpp acts as a global regulator of gene expression in bacteria. Proteomic analysis of cells lacking ppGpp has shown that this nucleotide might affect many more genes than previously anticipated. These findings and others suggest that ppGpp causes a redirection of transcription so that genes important for starvation survival and virulence are favoured at the expense of those required for growth and proliferation. In addition, new insights into the mechanism by which ppGpp affects gene expression have been achieved owing to in vitro studies of ppGpp function, complemented by structural studies of the ppGpp-RNA polymerase complex
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