Disease relevance of intI1

• The intI1 gene was present in 29.6% of the Enterobacteriaceae and in 21% of the Aeromonas isolates [1].
• PCR analysis with the conserved class 1 integron primers yielded amplicons of approximately 1 kb from E. coli isolates positive for intI1 and qacEDelta1 [2].
• Resolution of synthetic att-site Holliday structures by the integrase protein of bacteriophage lambda [3].
• lambda integrase (Int) mediates recombination between attachment sites on lambda phage and E. coli DNAs [4].
• Domains of the integrase protein of human immunodeficiency virus type 1 responsible for polynucleotidyl transfer and zinc binding [5].

High impact information on intI1

• A TYB-encoded protein, p90-TYB, contains amino acid sequences that are similar to those of retroviral integrase proteins [6].
• With the assistance of accessory proteins that induce DNA loops, Int bridges pairs of distinct arm- and core-type DNA binding sites to form synapsed recombination complexes, which then recombine via a Holliday junction (HJ) intermediate [4].
• These structures accommodate simultaneous binding of Int to direct-repeat arm sites and indirect-repeat core sites and afford a new view of the higher-order recombinogenic complexes [4].
• Integrase-mediated DNA cleavage before or immediately after synapsis is required to stabilize the synaptic assemblies [7].
• Conjugative transposition: Tn916 integrase contains two independent DNA binding domains that recognize different DNA sequences [8].

Chemical compound and disease context of intI1

• All sulphonamide resistant E. coli isolates were investigated for the presence of sul1, sul2, sul3 and intI1 genes by PCR [9].
• Holliday junctions (HJ) are the central intermediates in both homologous recombination and site-specific recombination performed by tyrosine recombinases such as the bacteriophage lambda Integrase (Int) protein [10].
• The oac gene encoding a lipopolysaccharide O-antigen acetylase maps adjacent to the integrase-encoding gene on the genome of Shigella flexneri bacteriophage Sf6 [11].

Biological context of intI1

• Integrons contain a gene coding for a lambda-like integrase that carries out site-specific recombination by interacting with two different target sites; the attI site and the palindromic sequence attC (59 base element) [12].
• Integrons confer on bacterial plasmids a capability of taking up antibiotic resistance genes by integrase-mediated recombination [13].
• Exploration of the genetic environment of oxa20 revealed the presence of the following integron features: (i) a second antibiotic resistance gene, aacA4; (ii) an intI1 gene; and (iii) two 59-base elements, each associated with either oxa20 or aacA4 [14].
• The VNTR assay was compared to XbaI pulsed-field gel electrophoresis, amplified fragment length polymorphism analysis, integron-cassette profiles and gene PCR of intI1, qacEDelta1, sulI1, and floR [15].
• Intl1 includes the four conserved amino acids that are characteristic of members of the integrase family, and Intl1 proteins with single amino acid substitutions at each of these positions had substantially reduced catalytic activity, consistent with this classification [16].

Anatomical context of intI1

• We also demonstrate that scIHF2 is stably expressed in HeLa cells, that it is localized primarily in the cell nucleus and that it triggers integrative recombination in mammalian cells by wild-type integrase [17].

Associations of intI1 with chemical compounds

• Interference by modified guanine and thymine residues in the DNA major groove and adenine residues in the minor groove were observed, indicating that the integrase interacts with both sides of the helix [12].
• We have used purified maltose-binding protein fused with the integrase (MBP-IntI1) and native IntI1 protein and gel retardation assays with fragments containing the complete and partial attI1 site to show formation of four complexes in this region [12].
• All 20 sul3 positive isolates were positive for intI1, and in 12 of these isolates sul3 was the only sulphonamide resistance gene detected [9].
• Determination of the presence of class 1 integrons indicated that 81% of the ciprofloxacin-resistant isolates contained an intI1 gene, compared with 11% of the ciprofloxacin-susceptible isolates (p<0.0001) [18].
• From this we have cloned and characterized a 188-amino acid, protease-resistant, carboxy-terminal fragment (C170) that we believe is the minimal catalytically competent domain of Int. C170 has topoisomerase activity and converts att suicide substrates to the covalent phosphotyrosine complexes characteristic of recombination intermediates [19].

Other interactions of intI1

• In colony hybridization experiments, both dhfrI and dhfrII were found associated with these integrase genes [20].
• Gene cassettes of class 1 integrons in Escherichia coli isolates from urine specimens collected in Korea during the last 2 decades were characterized. intI1 was detected in 54% of the isolates, yet gene cassette regions were amplified in only 43% of the isolates. intI2 was detected in 29 (5%) isolates, and no intI3 was detected in this study [21].
• Sixty-three percent of the clinical isolates were positive for the class 1 integron markers intI1 and qacEDelta1 [2].
• A larger protein, ORFAB, uses the same initiation codon and is produced by a -1 programmed translational frameshift between orfA and a downstream frame, orfB, whose amino acid sequence shows significant homology with retroviral integrase proteins [22].
• Among the sulI gene-positive strains, 96% were intI 1 gene positive [23].

Analytical, diagnostic and therapeutic context of intI1

• Furthermore, 52 isolates carried the integrase 1 gene and 24 strains gave five different PCR amplicon profiles using primers from the variable region of integron [24].
• It is proposed that C170 is likely to represent a generic Int family domain that thus affords a specific route to studying the chemistry of DNA cleavage and ligation in these recombinases [19].
• NMR titration data with a peptide corresponding to Xis residues 57-69 strongly suggest that the carboxyl-terminal tail of Xis and the alpha-helix of the aminoterminal domain of Int comprise the primary interaction surface for these two proteins [25].
• Thus, the phiBT1 bacteriophage integrase represents an effective site-specific genome integration system in mammalian cells and can be of great value in DNA-mediated gene therapy for a multitude of genetic disorders [26].
• Sequence analysis revealed the presence of an IS1 element between the int gene and the afa-3 gene cluster [27].

References