DomainSieve: a protein domain-based screen that led to the identification of dam-associated genes with potential link to DNA maintenance.
BACKGROUND
The Dam methyltransferase (DamMT) activity, broadly distributed in association with restriction endonucleases, as part of the restriction-modification defense systems, has evolved to become intimately associated with essential biological functions in a few organisms. In Escherichia coli, DamMT is involved in multiple aspects of DNA maintenance, replication initiation, daughter chromosome segregation, DNA mismatch repair, gene expression control, etc. The participation of DamMT in such a diverse set of functions required that other genes adapted, or emerged through evolution, in response to the DamMT-induced modification of the genomic environment. One example is SeqA, a protein that senses the methylation status of the origin of replication of the chromosome to control the timing of replication initiation. Interestingly, seqA is only present in a few DamMT-specifying proteobacteria. This observation led us to hypothesize that other genes, specifying related functions, might also be found in these organisms. To test this hypothesis, we implemented a large-scale comparative genomic screen meant to identify genes specifying DNA methylation sensing domains, probably involved in DNA maintenance functions.


RESULTS
We carried out a phylogenetic analysis of DamMT, identifying two contrasting behaviors of the protein. Based on this phylogeny, we defined precisely a set of genomes, in which the protein activity is likely to be involved in DNA maintenance functions, the 'resident' dam genomes. We defined a second set of genomes, in which DamMT is not resident. We developped a new tool, 'DomainSieve', in order to screen these two sets for protein domains that are strictly associated with 'resident' dam genomes. This approach was rewarding and generated a list of genes, among which some, at least, specify activities with clear linkage to DamMT-dependent DNA methylation and DNA maintenance.


BACKGROUND
DomainSieve is implemented as a web resource and is accessible at http://stat.genopole.cnrs.fr/ds/.
Brézellec
Pierre
P
Laboratoire Statistique et Génome du CNRS, Tour Evry 2, 523, Place des Terrasses de l'Agora, 91034 Evry Cedex, France.
Hoebeke
Mark
M
Hiet
Marie-Sophie
MS
Pasek
Sophie
S
Ferat
Jean-Luc
JL
D000465:Algorithms; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D020137:Base Pair Mismatch; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry*; D019175:DNA Methylation; D004260:DNA Repair; D004262:DNA Restriction Enzymes / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000378:metabolism; D016680:Genome, Bacterial; D008957:Models, Genetic; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics* / Q000502:physiology
D001425:Bacterial Outer Membrane Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C089746:SeqA protein, E coli; D004247:DNA; C058693:Dam methyltransferase; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D004262:DNA Restriction Enzymes