Disease relevance of dnaA

• Two regulatory regions containing nine and four copies of a repeating sequence, DnaA-box, which is identical with the DnaA protein-binding sequence repeated four times in the E. coli origin of replication, flank the 'dnaA' gene of B. subtilis [1].
• Salmonella bacteriophage P22 grows in two deoxyribonucleic acid initiation mutants of Escherichia coli under nonpermissive conditions, dnaA and dnaC [2].
• We have shown that the characteristic dnaA region is common among Escherichia coli (Gram-), Pseudomonas putida (Gram-), and Bacillus subtilis (low G + C Gram+) [3].
• Structure of the dnaA and DnaA-box region in the Mycoplasma capricolum chromosome: conservation and variations in the course of evolution [4].
• Structure of the dnaA region of Micrococcus luteus: conservation and variations among eubacteria [3].

High impact information on dnaA

• These and other observations are all consistent with the notion that hemimethylation in these two regions acts coordinately to ensure that every origin undergoes initiation once and only once per cell cycle; other possible roles for sequestration at dnaA are also considered [5].
• DNA replication was studied in a dnaA(Ts) strain containing a plasmid with the dnaA+ gene under plac control [6].
• Duplex opening by dnaA protein at novel sequences in initiation of replication at the origin of the E. coli chromosome [7].
• Regulatory influences on the effective action of the initiator protein of E. coli (dnaA protein) include transcriptional activation of the origin, nucleotide binding and membrane attachment of the protein, and interactions leading to the introduction of helicases to start replication forks [8].
• The dnaA gene in E. coli K-12 is required for the initiation of DNA replication [9].

Chemical compound and disease context of dnaA

• Over-expression of the groE operon in E. coli causes enhanced assembly of heterologously expressed ribulose bisphosphate carboxylase subunits and suppresses the heat-sensitive mutant phenotype of several dnaA alleles [10].
• Effect of dnaA and rpoB mutations on attenuation in the trp operon of Escherichia coli [11].
• ADP and ATP are tightly bound to dnaA protein and are crucial to its function in DNA replication; the exchange of these nucleotides is effected specifically by the acidic phospholipids (cardiolipin and phosphatidylglycerol) present in Escherichia coli membranes [Sekimizu, K. & Kornberg, A. (1988) J. Biol. Chem. 263, 7131-7135] [12].
• Inhibition of thymidine transport in dnaA mutants of Escherichia coli [13].
• Coumermycin A1-resistant E. coli were isolated and the mutation was mapped near dnaA [14].

Biological context of dnaA

• The organization of six open reading frames which were deduced from the nucleotide sequence of some 10 kb from the replication origin region of Bacillus subtilis resembles the organization of the genes in the rnpA-dnaA-gyrB region of the Escherichia coli chromosome [1].
• The nucleotide sequence was determined of a 945-bp EcoRI fragment from the Escherichia coli K-12 chromosome at 82 min containing the promoter region of the dnaA gene [15].
• DNA gyrase on the bacterial chromosome. Oxolinic acid-induced DNA cleavage in the dnaA-gyrB region [16].
• The dnaA/dnaN intergenic region (273 bp) identified to be the minimal oriC region responsible for autonomous replication has 10 pure AT clusters of four to seven bases and only three consensus DnaA boxes [17].
• Examination of the intercistronic sequence and analysis of in vitro transcription supported the notion that the dnaA and dnaN genes constitute a single operon [18].

Anatomical context of dnaA

• Altered biological properties of cell membranes in Escherichia coli dnaA and seqA mutants [19].
• We previously reported that mutations in the dnaA gene which encodes the initiator of chromosomal DNA replication in Escherichia coli caused an alteration in the levels of unsaturated fatty acids of phospholipids in membranes [20].

Associations of dnaA with chemical compounds

• A 54 kD and a 91 kD polypeptide appear to be coded for by the dnaA and gyrB genes, respectively; the 91 kD protein is encoded on a region in which coumermycin sensitivity maps and is with respect to electrophoretic behavior identical to subunit B of DNA gyrase [21].
• DNAase protection experiments showed that the dnaA protein binds to DNA in the region of the two dnaA promoters [9].
• The dnaA mutations that suppress the dnaZ(TS) defect are designated dnaA(SUZ, CS) [22].
• An improved, rapid procedure for purifying dnaA protein from overproducing cells appears to depend on its coprecipitation with phospholipids and depends on solubilization by guanidine HCl [23].
• The activity of the mutated dnaA protein at the tryptophan attenuator and its activity as initiator for chromosome replication decreased gradually with increasing temperature [11].

Physical interactions of dnaA

• Using filter binding assays, dnaA protein was observed to bind specifically to DNA fragments containing the rpoH promoter region with greater affinity than its binding to the dnaA promoter region [24].
• Essential role of the gyrB gene product in the transcriptional event coupled to dnaA-dependent initiation of Escherichia coli chromosome replication [25].

Regulatory relationships of dnaA

• Using translational fusions to lacZ we found that DNA damage caused by mitomycin C induces expression of the dnaA and dnaQ genes [26].
• In exponentially growing cells, dnaN and recF are expressed predominantly from the dnaA promoters [27].
• Particular mutations in the rpoB gene were able to suppress negative effects that certain dnaA mutations had on the replication of lambda plasmids; this suppression was allele-specific [28].
• dnaA protein regulates transcriptions of the rpoH gene of Escherichia coli [24].

Other interactions of dnaA

• The rpmH gene and the dnaA gene are transcribed in the clockwise and counter-clockwise direction, respectively [15].
• One such suppressor, named sueA77, was finely mapped and found to be located at 82 min on the E. coli chromosome, between dnaA and recF, and within the dnaN gene [Sakakibara, Y. & Mizukami, T. (1980) Mol. Gen. Genet. 178, 541-553] [29].
• There are at least three dnaN promoters located in the second half of the dnaA coding region [30].
• Termination of the Escherichia coli asnC transcript. The DnaA protein/dnaA box complex blocks transcribing RNA polymerase [31].
• The decrease in the expression of dnaA was measured in vivo using a dnaA-lacZ gene fusion [32].

Analytical, diagnostic and therapeutic context of dnaA

• Titration of DnaA protein by oriC DnaA-boxes increases dnaA gene expression in Escherichia coli [33].
• Immunoassays of dnaA protein in extracts from five strains showed a rather constant abundance relative to cell mass, with a variation of 800-2100 molecules/cell; overproducing cells contained 100-fold that number [23].
• Folded chromosomes were isolated from Eschericia coli thermosensitive dnaA initiation mutants incubated at the nonpermissive temperature and were analyzed by neutral sucrose density gradient centrifugation [34].
• Sequence analysis of a 34.7-kb DNA segment from the genome of Buchnera aphidicola (endosymbiont of aphids) containing groEL, dnaA, the atp operon, gidA, and rho [35].
• Pulsed-field gel electrophoresis and Southern blot analyses indicated that both the dnaA and dnaK gene regions exist as single copies on the 3.4 Mb chromosome [36].

References