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Escherichia coli YafP protein modulates DNA damaging property of the nitroaromatic compounds.

Gutierrez A, Elez M, Clermont O, Denamur E, Matic I - Nucleic Acids Res. (2011)

Bottom Line: Using a murine septicaemia model, we showed that YafP activity reduced the bacterial fitness in the absence of PolIV.The YafP antimutator activity was independent of the PolIV activity.Given that YafP was annotated as a putative acetyltransferase, it could be that YafP participates in the metabolic transformation of genotoxic compounds, hence modulating the balance between their mutagenicity and cytotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Faculté de Médecine Paris Descartes, Inserm U1001, Université Paris Descartes, Paris, France.

ABSTRACT
Escherichia coli SOS functions constitute a multifaceted response to DNA damage. We undertook to study the role of yafP, a SOS gene with unknown function. yafP is part of an operon also containing the dinB gene coding for DNA Polymerase IV (PolIV). Our phylogenetic analysis showed that the gene content of this operon is variable but that the dinB and the yafP genes are conserved in the majority of E. coli natural isolates. Therefore, we studied if these proteins are functionally linked. Using a murine septicaemia model, we showed that YafP activity reduced the bacterial fitness in the absence of PolIV. Similarly, YafP increased cytotoxicity of two DNA damaging nitroaromatic compounds, 4-nitroquinoline-1-oxide (NQO) and nitrofurazone, in the absence of PolIV. The fact that PolIV counterbalances YafP-induced cytotoxicity could explain why these two genes are transcriptionally linked. We also studied the involvement of YafP in genotoxic-stress induced mutagenesis and found that PolIV and YafP reduced NQO-induced mutagenicity. The YafP antimutator activity was independent of the PolIV activity. Given that YafP was annotated as a putative acetyltransferase, it could be that YafP participates in the metabolic transformation of genotoxic compounds, hence modulating the balance between their mutagenicity and cytotoxicity.

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Phylogenetic analysis of the dinB, yafN, yafO and yafP operon within the E. coli species. (A) Schematic representation of the four-gene operon as found in E. coli K-12 MG1655 and E. fergusonii and the two-gene operon as found in E. coli CFT073. In the latter case, dinB and yafP genes are fused together and overlap by four nucleotides, i.e., ATGA (B) Structure of the dinB operon in genomes of the strains from ECOR collection representative of the E. coli strain phylogeny. The strain phylogenic tree was reconstructed from MLST data (20). Numbers at nodes represent bootstrap values superior to 70%. Strains labelled in red or blue possess either the four-genes operons or the two-genes operons, respectively. The four strains labelled in black correspond to strains whose operons were not analyzed for following reasons: ECOR 9 strain has an insertion sequence in the dinB genes leading to a non-functional operon, and ECOR 5, 64, 47 strains for which no PCR amplification was obtained suggesting that dinB operon region could be rearranged or deleted.
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Figure 1: Phylogenetic analysis of the dinB, yafN, yafO and yafP operon within the E. coli species. (A) Schematic representation of the four-gene operon as found in E. coli K-12 MG1655 and E. fergusonii and the two-gene operon as found in E. coli CFT073. In the latter case, dinB and yafP genes are fused together and overlap by four nucleotides, i.e., ATGA (B) Structure of the dinB operon in genomes of the strains from ECOR collection representative of the E. coli strain phylogeny. The strain phylogenic tree was reconstructed from MLST data (20). Numbers at nodes represent bootstrap values superior to 70%. Strains labelled in red or blue possess either the four-genes operons or the two-genes operons, respectively. The four strains labelled in black correspond to strains whose operons were not analyzed for following reasons: ECOR 9 strain has an insertion sequence in the dinB genes leading to a non-functional operon, and ECOR 5, 64, 47 strains for which no PCR amplification was obtained suggesting that dinB operon region could be rearranged or deleted.

Mentions: The genome sequences of 98 E. coli (including eight Shigella) strains are currently available at the NCBI genome database (http://www.ncbi.nlm.nih.gov/genomes). Database searches showed that dinB, yafN, yafO and yafP operon structure found in standard laboratory E. coli K-12 strain is not conserved across E. coli species. While, 60% of strains have the four-gene operon, 40% have only dinB and yafP genes. In this latter case, dinB and yafP genes are always fused together and overlap by 4 nt, i.e. ATGA (Figure 1A). The termination codon of dinB overlaps with the initiation codon of yafP. This structure of two-gene operon probably resulted from the recombination between two ATGA sequences present in the four-gene operon resulting in deletion of yafN and yafO genes.Figure 1.


Escherichia coli YafP protein modulates DNA damaging property of the nitroaromatic compounds.

Gutierrez A, Elez M, Clermont O, Denamur E, Matic I - Nucleic Acids Res. (2011)

Phylogenetic analysis of the dinB, yafN, yafO and yafP operon within the E. coli species. (A) Schematic representation of the four-gene operon as found in E. coli K-12 MG1655 and E. fergusonii and the two-gene operon as found in E. coli CFT073. In the latter case, dinB and yafP genes are fused together and overlap by four nucleotides, i.e., ATGA (B) Structure of the dinB operon in genomes of the strains from ECOR collection representative of the E. coli strain phylogeny. The strain phylogenic tree was reconstructed from MLST data (20). Numbers at nodes represent bootstrap values superior to 70%. Strains labelled in red or blue possess either the four-genes operons or the two-genes operons, respectively. The four strains labelled in black correspond to strains whose operons were not analyzed for following reasons: ECOR 9 strain has an insertion sequence in the dinB genes leading to a non-functional operon, and ECOR 5, 64, 47 strains for which no PCR amplification was obtained suggesting that dinB operon region could be rearranged or deleted.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105422&req=5

Figure 1: Phylogenetic analysis of the dinB, yafN, yafO and yafP operon within the E. coli species. (A) Schematic representation of the four-gene operon as found in E. coli K-12 MG1655 and E. fergusonii and the two-gene operon as found in E. coli CFT073. In the latter case, dinB and yafP genes are fused together and overlap by four nucleotides, i.e., ATGA (B) Structure of the dinB operon in genomes of the strains from ECOR collection representative of the E. coli strain phylogeny. The strain phylogenic tree was reconstructed from MLST data (20). Numbers at nodes represent bootstrap values superior to 70%. Strains labelled in red or blue possess either the four-genes operons or the two-genes operons, respectively. The four strains labelled in black correspond to strains whose operons were not analyzed for following reasons: ECOR 9 strain has an insertion sequence in the dinB genes leading to a non-functional operon, and ECOR 5, 64, 47 strains for which no PCR amplification was obtained suggesting that dinB operon region could be rearranged or deleted.
Mentions: The genome sequences of 98 E. coli (including eight Shigella) strains are currently available at the NCBI genome database (http://www.ncbi.nlm.nih.gov/genomes). Database searches showed that dinB, yafN, yafO and yafP operon structure found in standard laboratory E. coli K-12 strain is not conserved across E. coli species. While, 60% of strains have the four-gene operon, 40% have only dinB and yafP genes. In this latter case, dinB and yafP genes are always fused together and overlap by 4 nt, i.e. ATGA (Figure 1A). The termination codon of dinB overlaps with the initiation codon of yafP. This structure of two-gene operon probably resulted from the recombination between two ATGA sequences present in the four-gene operon resulting in deletion of yafN and yafO genes.Figure 1.

Bottom Line: Using a murine septicaemia model, we showed that YafP activity reduced the bacterial fitness in the absence of PolIV.The YafP antimutator activity was independent of the PolIV activity.Given that YafP was annotated as a putative acetyltransferase, it could be that YafP participates in the metabolic transformation of genotoxic compounds, hence modulating the balance between their mutagenicity and cytotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Faculté de Médecine Paris Descartes, Inserm U1001, Université Paris Descartes, Paris, France.

ABSTRACT
Escherichia coli SOS functions constitute a multifaceted response to DNA damage. We undertook to study the role of yafP, a SOS gene with unknown function. yafP is part of an operon also containing the dinB gene coding for DNA Polymerase IV (PolIV). Our phylogenetic analysis showed that the gene content of this operon is variable but that the dinB and the yafP genes are conserved in the majority of E. coli natural isolates. Therefore, we studied if these proteins are functionally linked. Using a murine septicaemia model, we showed that YafP activity reduced the bacterial fitness in the absence of PolIV. Similarly, YafP increased cytotoxicity of two DNA damaging nitroaromatic compounds, 4-nitroquinoline-1-oxide (NQO) and nitrofurazone, in the absence of PolIV. The fact that PolIV counterbalances YafP-induced cytotoxicity could explain why these two genes are transcriptionally linked. We also studied the involvement of YafP in genotoxic-stress induced mutagenesis and found that PolIV and YafP reduced NQO-induced mutagenicity. The YafP antimutator activity was independent of the PolIV activity. Given that YafP was annotated as a putative acetyltransferase, it could be that YafP participates in the metabolic transformation of genotoxic compounds, hence modulating the balance between their mutagenicity and cytotoxicity.

Show MeSH
Related in: MedlinePlus