The Verrucomicrobia LexA-Binding Motif : Insights into the Evolutionary Dynamics of the SOS Response
Erill, Ivan (University of Maryland Baltimore County. Erill Lab, Department of Biological Sciences)
Campoy Sánchez, Susana (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Kiliç, Sefa (University of Maryland Baltimore County. Erill Lab, Department of Biological Sciences)
Barbé García, Jordi (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Fecha:	2016
Resumen:	The SOS response is the primary bacterial mechanism to address DNA damage, coordinating multiple cellular processes that include DNA repair, cell division, and translesion synthesis. In contrast to other regulatory systems, the composition of the SOS genetic network and the binding motif of its transcriptional repressor, LexA, have been shown to vary greatly across bacterial clades, making it an ideal system to study the co-evolution of transcription factors and their regulons. Leveraging comparative genomics approaches and prior knowledge on the core SOS regulon, here we define the binding motif of the Verrucomicrobia, a recently described phylum of emerging interest due to its association with eukaryotic hosts. Site directed mutagenesis of the Verrucomicrobium spinosum recA promoter confirms that LexA binds a 14 bp palindromic motif with consensus sequence TGTTC-N4-GAACA. Computational analyses suggest that recognition of this novel motif is determined primarily by changes in base-contacting residues of the third alpha helix of the LexA helix-turn-helix DNA binding motif. In conjunction with comparative genomics analysis of the LexA regulon in the Verrucomicrobia phylum, electrophoretic shift assays reveal that LexA binds to operators in the promoter region of DNA repair genes and a mutagenesis cassette in this organism, and identify previously unreported components of the SOS response. The identification of tandem LexA-binding sites generating instances of other LexA-binding motifs in the lexA gene promoter of Verrucomicrobia species leads us to postulate a novel mechanism for LexA-binding motif evolution. This model, based on gene duplication, successfully addresses outstanding questions in the intricate co-evolution of the LexA protein, its binding motif and the regulatory network it controls.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	SOS response ; LexA regulon ; DNA repair ; Comparative genomics ; Binding motif ; Translesion synthesis ; Uracil-dna glycosylase ; Regulatory network evolution
Publicado en:	Frontiers in Molecular Biosciences, Vol. 3 (july 2016) , art. 33, ISSN 2296-889X

DOI: 10.3389/fmolb.2016.00033
PMID: 27489856

13 p, 5.2 MB

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