title: Escherichia coli YafP protein modulates DNA damaging property of the nitroaromatic compounds.
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.
authors.affiliation: Faculté de Médecine Paris Descartes, Inserm U1001, Université Paris Descartes, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Marina
authors.initials: M
authors.lastname: Elez
authors.forename: Olivier
authors.initials: O
authors.lastname: Clermont
authors.forename: Erick
authors.initials: E
authors.lastname: Denamur
authors.forename: Ivan
authors.initials: I
authors.lastname: Matic
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000235:genetics; D004926:Escherichia coli / Q000145:classification / Q000235:genetics; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D050296:Microbial Viability; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009583:Nitrofurazone / Q000633:toxicity*; D009876:Operon; D010802:Phylogeny
chemical_list: C094399:DinB protein, E coli; D029968:Escherichia coli Proteins; D009153:Mutagens; D015112:4-Nitroquinoline-1-oxide; D000123:Acetyltransferases; C560089:YafP protein, E coli; D019951:DNA Polymerase beta; D009583:Nitrofurazone