|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
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
|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].
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.
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
dndDB 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.