Introduction References
Introduction to dndDB
H.Y. Ou, X. He, Y. Shao, C. Tai, K. Rajakumar and Z. Deng (2009) dndDB: a database focused on phosphorothioation of the DNA backbone. PLoS ONE, 4, e5132. [dndDB website] [Abstract]

The purpose of dndDB is to provide a user-friendly interactive platform not only to efficiently archive, analyse and manipulate increasing data about bacterial and archeal dnd genes, linked island-borne genes, matching sets of cognate proteins, and the DNA phosphorothioation process itself, but to also empower researchers from different backgrounds to explore novel angels potentially related to this, thus far, unique DNA backbone modification process. A broad range of similarity search, sequence alignment and phylogenetic tools are readily accessible to allow for user-directed interrogation of the database, examination of user-supplied sequences and other individualized directions of research.

The DNA degradation (Dnd) phenotype encoded by dnd gene cluster was first observed during electrophoresis of genomic DNA from Streptomyces lividans, and subsequently found to be widespread among many other distantly related bacteria [Zhou et al. (1988) Nucleic Acids Res. 16, 4341-4352; Zhou et al. (2005). Mol. Microbiol., 57, 1428-1438]. It was thought to involve a post-replicative DNA modification that rendered the DNA susceptible to degradation at the electrophoretic anode [Dyson, P. & Evans, M. (1998) Nucleic Acids Res. 26, 1248–1253.]. In 2005 the five-gene S. lividans dnd cluster responsible for this phenotype was described. Intriguingly, to date all identified dnd clusters lie within larger genomic islands, fragments of alien DNA that have been incorporated into genomes of new hosts via horizontal transfer events [Zhou et al. (2004) Appl Environ Microb, 70, 7110-7118; He et al. (2007) Mol. Microbiol., 65, 1034-1048 ; Ou et al (2007). Nucleic Acids Res. 35, W97-W104].
 
dnd gene clusters in 12 bacterial genomic islands and plasmid

More recently the dnd cluster was shown to mediate the incorporation of sulphur into the DNA backbone via a sequence-selective, stereo-specific phosphorothioate modification [Wang et al. (2007). Nature Chem. Bio., 3, 709-710]. This is the first report of natural modification of the DNA backbone itself and sets it apart from well-documented DNA methylation and other changes to DNA bases.
"SULFUR SURPRISE: This dinucleotide, which occurs naturally in bacterial genomic DNA, possesses a sulfur atom in place of one of the nonbridging oxygen atoms on its phosphate group". Reported by Chemical & Engineering News Oct. 22, 2007, 14.
We are currently organizing all available experimental and bioinformatics analyses data and documentation about known dnd gene clusters and the DNA phosphorothioation phenomenon as a MySQL database called dndDB which is freely available at the website http://mml.sjtu.edu.cn/dndDB/.

dnd
DB contains detailed information about the following: (i) Dnd phenotype; (ii) dnd gene clusters; (iii) genomic islands harbouring dnd genes; (iv) Dnd proteins and conserved domains. In addition, brief descriptions of ongoing research into the dnd system by our group and collaborators are also incorporated into dndDB. These will include work on a putative Dnd-dependent restriction-modification system, the precise nature of the DNA modification itself, the core sequence motif that targets the site-specific modification in S. lividans and the increasingly well characterized novel biochemical pathway that mediates this unique biological process.

As of 28 June 2008 dndDB contains details of 19 syntenic dnd clusters in 18 species of Eubacteria and Archaea. Additionally, we will shortly be uploading a much larger set of sequences which exhibit homology to isolated members of the dnd cluster. We will continue to identify additional syntenic clusters and isolated dnd-like genes as gene, genome and metagenome databases expand and anticipate providing a pipeline for ready automated discovery of dnd clusters. Users can search dndDB by dnd gene, protein or organism names and are able to blast a query sequence against dndDB to find homologous matches. A broad range of similarity search, sequence alignment and phylogenetic tools are readily accessible to allow for user-directed analyses focused on dnd genes to facilitate individualized directions of research.

As future developments, we will shortly be uploading a large set of sequences which exhibit homology to isolated dnd genes, as apposed to dnd clusters only, and a further set corresponding to homologues of the full complement of non-dnd genes borne on dnd islands. We will continue to identify additional syntenic clusters, isolated dnd-like genes and other dnd island gene homologues as gene, genome and metagenome databases expand, and anticipate eventually providing a pipeline for ready automated discovery, annotation and analyses of dnd genes, clusters and associated genomic islands.


Ultimately, we envisage a resource that seeks to effectively combine and interlink the genetics, biochemistry and functional aspects of the dnd system to facilitate efficient investigation of a wide range of aspects relating to the dnd DNA modification process in diverse host organisms. We believe that the lessons learnt from ongoing dissection of the dnd system will provide clues to resolve mysteries relating to weakly similar genes, proteins and biochemical reactions, and in due course give rise to novel biotechnological and/or clinical applications; thus we expect that dndDB will prove to be of interest to a broad community of researchers.
 
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References
1.  Wang, LR; Chen, S; Xu, TG; Taghizadeh, K; Wishnok, JS; Zhou, XF; You, DL; Deng, ZX; Dedon, PC  (2007).  Phosphorothioation of DNA in bacteria by dnd genes.  NATURE CHEMICAL BIOLOGY,   3:709-710.  [Abstract]  [Full Text]  (Featured by Fritz Eckstein in Nat Chem Biol. 2007 3(11):689-690 [Full Text ] and Reported by Chemical & Engineering News Oct. 22, 2007, 14)
2.  He, X; Ou, HY; Yu, Q; Zhou, X; Wu, J; Liang, J; Zhang, W; Rajakumar, K; Deng, Z  (2007).  Analysis of a genomic island housing genes for DNA S-modification system in Streptomyces lividans 66.  MOLECULAR MICROBIOLOGY,   65:1034-1048.  [Abstract]  [Full Text] 
3.  Liang, JD; Wang, ZJ; He, XY; Li, JL; Zhou, XF; Deng, ZX  (2007).  DNA modification by sulfur: analysis of the sequence recognition specificity surrounding the modification sites.  NUCLEIC ACIDS RESEARCH,   35:2944-2954.  [Abstract]  [Full Text] 
4.  You, DL; Wang, LR; Yao, F; Zhou, XF; Deng, ZX  (2007).  A novel DNA modification by sulfur: DndA is a NifS-like cysteine desulfurase capable of assembling DndC as an iron-sulfur cluster protein in Streptomyces lividans.  BIOCHEMISTRY,   46:6126-6133.  [Abstract]  [Full Text] 
5.  Ou, HY; He, XY; Harrison, EM; Kulasekara, BR; Bin Thani, A; Kadioglu, A; Lory, S; Hinton, JCD; Barer, MR; Deng, ZX; Rajakumar, K  (2007).  MobilomeFINDER: web-based tools for in silico and experimental discovery of bacterial genomic islands.  NUCLEIC ACIDS RESEARCH,   35:W97-W104.  [Abstract]  [Full Text]  [MobilomeFINDER webserver]
6.  Zhou, XF; He, XY; Liang, JD; Li, AY; Xu, TG; Kieser, T; Helmann, JD; Deng, ZX  (2005).  A novel DNA modification by sulphur.  MOLECULAR MICROBIOLOGY,   57:1428-1438.  [Abstract]  [Full Text] 
7.  Zhou, XF; He, XY; Li, AY; Lei, F; Kieser, T; Deng, ZX  (2004).  Streptomyces coelicolor A3(2) lacks a genomic island present in the chromosome of Streptomyces lividans 66.  APPLIED AND ENVIRONMENTAL MICROBIOLOGY,   70:7110-7118.  [Abstract]  [Full Text] 
8.  Zhou, X; Deng, Z; Firmin, J L; Hopwood, D A; Kieser, T  (1988).  Site-specific degradation of Streptomyces lividans DNA during electrophoresis in buffers contaminated with ferrous iron.  NUCLEIC ACIDS RESEARCH,   16:4341-4352 .  [Abstract]  [Full Text] 
9.  Yao, F; Xu, T; Zhou, X; Deng, Z; You, D  (2009).  Functional analysis of spfD gene involved in DNA phosphorothioation in Pseudomonas fluorescens Pf0-1.  FEBS Letters,   :-.  [Abstract]  [Full Text] 
10.  Xu, T; Liang, J; Chen, S; Wang, L; He, X; You, D; Wang, Z; Li, A; Xu, Z; Zhou, X; Deng, Z  (2009).  DNA phosphorothioation in Streptomyces lividans: Mutational analysis of the dnd locus.  BMC Microbiol,   :-.  [Abstract]  [Full Text] 
11.  Wang L, Chen S, Vergin KL, Giovannoni SJ, Chan SW, DeMott MS, Taghizadeh K, Cordero OX, Cutler M, Timberlake S, Alm EJ, Polz MF, Pinhassi J, Deng Z, Dedon PC.  (2011).  DNA phosphorothioation is widespread and quantized in bacterial genomes.  Proc Natl Acad Sci U S A,   108:2963-2968.  [Abstract]  [Full Text] 
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