A mutant cysteinyl-tRNA synthetase affecting timing of chromosomal replication initiation in B. subtilis and conferring resistance to a protein kinase C inhibitor.

Séror, Simone J.; Casarégola, Serge; Vannier, Françoise; Zouari, N.; Dahl, Michael K.; Boye, Erik

doi:10.1002/j.1460-2075.1994.tb06532.x

Cited by 23 publications

(16 citation statements)

References 69 publications

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“…Incubation was continued for a further 5 h to complete ongoing replication. A previous paper reported that this drug inhibited replication initiation and cell division simultaneously in B. subtilis cells (40). In fact, the cell length at initiation estimated by flow cytometry corresponded approximately to that obtained previously by an extensive microscopic analysis (41) (data not shown).…”

Section: Methodssupporting

confidence: 86%

Autoregulation of the dnaA-dnaN Operon and Effects of DnaA Protein Levels on Replication Initiation in Bacillus subtilis

et al. 2001

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In Escherichia coli, the DnaA protein level appears to play a pivotal role in determining the timing of replication initiation. To examine the effects on replication initiation in B. subtilis, we constructed a strain in which a copy of the dnaA gene was integrated at the purA locus on the chromosome under the control of an isopropyl-␤-D-thiogalactopyranoside (IPTG)-inducible promoter. However, increasing the DnaA level resulted in cell elongation and inhibition of cell growth by induction of the SOS response. Transcription of the native dnaA-dnaN operon was greatly reduced at high DnaA levels, but it was increased in a dnaA-null mutant, indicating autoregulation of the operon by DnaA. When a copy of the dnaN gene was added downstream of the additional dnaA gene at purA, the cells grew at high DnaA levels, suggesting that depletion of DnaN (␤ subunit of DNA polymerase III) within the cell by repression of the native dnaA-dnaN operon at high DnaA levels was the cause of the SOS induction. Flow cytometry of the cells revealed that the cell mass at initiation of replication increased at a lower DnaA level and decreased at DnaA levels higher than those of the wild type. Proper timing of replication initiation was observed at DnaA levels nearly comparable to the wild-type level. These results suggest that if the DnaA level increases with progression of the replication cycle, it could act as a rate-limiting factor of replication initiation in B. subtilis.

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Section: Methodssupporting

confidence: 86%

Autoregulation of the dnaA-dnaN Operon and Effects of DnaA Protein Levels on Replication Initiation in Bacillus subtilis

et al. 2001

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“…In E. coli and B. subtilis , when Rif are added to the culture, RNA synthesis is inhibited, whereas DNA synthesis continues until all cells complete replication and end up with fully replicated chromosomes. DNA plots of Rif‐treated E. coli and B. subtilis cultures show peaks which correspond to the cell ploidy (Skarstad et al ., ; Seror et al ., ). Our result was similar to those in E. coli and B. subtilis , suggesting that Rif inhibits the initiation but not the progression of DNA replication in S .…”

Section: Resultsmentioning

confidence: 97%

DNA replication depends on photosynthetic electron transport in cyanobacteria

Ohbayashi

Watanabe

Kanesaki

et al. 2013

FEMS Microbiol Lett

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The freshwater cyanobacterium Synechococcus elongatus PCC 7942 exhibits light-dependent growth. Although it has been reported that DNA replication also depends on light irradiation in S. elongatus 7942, the involvement of the light in the regulation of DNA replication remains unclear. To elucidate the regulatory pathway of DNA replication by light, we studied the effect of several inhibitors, including two electron transport inhibitors, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), on DNA replication in S. elongatus 7942. DCMU inhibited only DNA replication initiation, whereas DBMIB blocked both the initiation and progression of DNA replication. These results suggest that DNA replication depends on the photosynthetic electron transport activity and initiation and progression of DNA replication are regulated in different ways.

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“…Consistent with its potential DNA binding property, the P. falciparum PheRS (PFA0480w) has a nuclear localization signal. The CysRS of B. subtilis (which also contains a DNA binding domain) is believed to play a role in initiating chromosomal replication [58]. Therefore, functional roles for P. falciparum PheRSs may extend from aminoacylation to DNA recognition and replication - a suggestion that requires experimental investigation.…”

Section: Resultsmentioning

confidence: 99%

A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium falciparum

et al. 2009

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BackgroundPlasmodium parasites are causative agents of malaria which affects >500 million people and claims ~2 million lives annually. The completion of Plasmodium genome sequencing and availability of PlasmoDB database has provided a platform for systematic study of parasite genome. Aminoacyl-tRNA synthetases (aaRSs) are pivotal enzymes for protein translation and other vital cellular processes. We report an extensive analysis of the Plasmodium falciparum genome to identify and classify aaRSs in this organism.ResultsUsing various computational and bioinformatics tools, we have identified 37 aaRSs in P. falciparum. Our key observations are: (i) fraction of proteome dedicated to aaRSs in P. falciparum is very high compared to many other organisms; (ii) 23 out of 37 Pf-aaRS sequences contain signal peptides possibly directing them to different cellular organelles; (iii) expression profiles of Pf-aaRSs vary considerably at various life cycle stages of the parasite; (iv) several PfaaRSs posses very unusual domain architectures; (v) phylogenetic analyses reveal evolutionary relatedness of several parasite aaRSs to bacterial and plants aaRSs; (vi) three dimensional structural modelling has provided insights which could be exploited in inhibitor discovery against parasite aaRSs.ConclusionWe have identified 37 Pf-aaRSs based on our bioinformatics analysis. Our data reveal several unique attributes in this protein family. We have annotated all 37 Pf-aaRSs based on predicted localization, phylogenetics, domain architectures and their overall protein expression profiles. The sets of distinct features elaborated in this work will provide a platform for experimental dissection of this family of enzymes, possibly for the discovery of novel drugs against malaria.

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A mutant cysteinyl-tRNA synthetase affecting timing of chromosomal replication initiation in B. subtilis and conferring resistance to a protein kinase C inhibitor.

Cited by 23 publications

References 69 publications

Autoregulation of the dnaA-dnaN Operon and Effects of DnaA Protein Levels on Replication Initiation in Bacillus subtilis

Autoregulation of the dnaA-dnaN Operon and Effects of DnaA Protein Levels on Replication Initiation in Bacillus subtilis

DNA replication depends on photosynthetic electron transport in cyanobacteria

A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium falciparum

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