title: Clp-dependent proteolysis of the LexA N-terminal domain in Staphylococcus aureus.
abstract: The SOS response is governed by the transcriptional regulator LexA and is elicited in many bacterial species in response to DNA damaging conditions. Induction of the SOS response is mediated by autocleavage of the LexA repressor resulting in a C-terminal dimerization domain (CTD) and an N-terminal DNA-binding domain (NTD) known to retain some DNA-binding activity. The proteases responsible for degrading the LexA domains have been identified in Escherichia coli as ClpXP and Lon. Here, we show that in the human and animal pathogen Staphylococcus aureus, the ClpXP and ClpCP proteases contribute to degradation of the NTD and to a lesser degree the CTD. In the absence of the proteolytic subunit, ClpP, or one or both of the Clp ATPases, ClpX and ClpC, the LexA domains were stabilized after autocleavage. Production of a stabilized variant of the NTD interfered with mitomycin-mediated induction of sosA expression while leaving lexA unaffected, and also significantly reduced SOS-induced mutagenesis. Our results show that sequential proteolysis of LexA is conserved in S. aureus and that the NTD may differentially regulate a subset of genes in the SOS regulon.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
authors.forename: Marianne T
authors.initials: MT
authors.lastname: Cohn
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Kjelgaard
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Frees
authors.affiliation: Departamento de Quimica, Bioquimica y Biologia Molecular, Universidad Cardenal Herrera-CEU, Moncada, Valencia 46113, Spain.|Centro Investigación y Tecnologia Animal, Instituto Valenciano de Investigaciones Agrarias (CITA-IVIA), Apdo 187, Segorbe, Castellón, Spain.
authors.forename: José R
authors.initials: JR
authors.lastname: Penadés
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Ingmer
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D049071:Endopeptidase Clp / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013014:SOS Response, Genetics; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D000099160:LexA Repressor Protein
chemical_list: D001426:Bacterial Proteins; D049071:Endopeptidase Clp; D016685:Mitomycin; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein