title: Regulation of DNA phosphorothioate modification in Salmonella enterica by DndB.
abstract: DNA phosphorothioate (PT) modification, in which the non-bridging oxygen of the sugar-phosphate backbone is substituted by sulfur, occurs naturally in diverse bacteria and archaea and is regulated by the DndABCDE proteins. DndABCDE and the restriction cognate DndFGHI constitute a new type of defense system that prevents the invasion of foreign DNA in Salmonella enterica serovar Cerro 87. GAAC/GTTC consensus contexts across genomes were found to possess partial PT modifications even in the presence of restriction activity, indicating the regulation of PT. The abundance of PT in cells must be controlled to suit cellular activities. However, the regulatory mechanism of PT modification has not been characterized. The result here indicated that genomic PT modification in S. enterica is controlled by the transcriptional regulator DndB, which binds to two regions in the promoter, each possessing a 5'-TACGN(10)CGTA-3' palindromic motif, to regulate the transcription of dndCDE and its own gene. Site-directed mutagenesis showed that the Cys29 residue of DndB plays a key role in its DNA-binding activity or conformation. Proteomic analysis identified changes to a number of cellular proteins upon up-regulation and loss of PT. Considering the genetic conservation of dnd operons, regulation of PT by DndB might be widespread in diverse organisms.
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: 1] Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China [2] Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: You
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Chan
authors.affiliation: 1] Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China [2] Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Lianrong
authors.initials: L
authors.lastname: Wang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D004269:DNA, Bacterial / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D055029:Inverted Repeat Sequences; D009154:Mutation; D059372:Nucleotide Motifs; D009876:Operon; D011485:Protein Binding; D020543:Proteome; D040901:Proteomics; D019779:Salmonella enterica / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D020543:Proteome