Disease relevance of Replicon

• The mouse mitochondrial DNA genome has been cloned in Escherichia coli by linking it to the pSC101 plasmid replicon at cohesive-ended cleavage sites generated by Eco Rl restriction endonuclease [1].
• Here, we describe a novel, naked DNA vaccine encoding an alphavirus replicon (self-replicating mRNA) and the self/tumor antigen tyrosinase-related protein-1 [2].
• Cytokine production in motor neurons by poliovirus replicon vector gene delivery [3].
• We have developed Sindbis virus replicon particles that express the measles virus (MV) hemagglutinin (SIN-H) or fusion (SIN-F) proteins [4].
• The ResT protein, a telomere resolvase from Borrelia burgdorferi, processes replication intermediates into linear replicons with hairpin ends by using a catalytic mechanism similar to that for tyrosine recombinases and type IB topoisomerases [5].

Psychiatry related information on Replicon

• The high permissiveness of the cured cells for the replicon was abolished by transgenic supplementation of IRF-1 expression [6].

High impact information on Replicon

• F plasmid provides a function that promotes recA-independent site-specific fusions of pSC101 replicon [7].
• Thus, Nbs1 suppresses rereplication of cellular DNA and SV40 origin-containing replicons, and T targets Nbs1, thereby enhancing the yield of new SV40 genomes during viral DNA replication [8].
• We propose that ATR and ATM regulate SPK activity through a feedback mechanism originating at active replicons [9].
• Timing of DNA replication initiation is dependent on S-phase-promoting kinase (SPK) activity at discrete origins and the simultaneous function of many replicons [9].
• Saccharomyces cerevisiae is host to the dsRNA viruses L-A (including its killer toxin-encoding satellite, M) and L-BC, the 20S and 23S ssRNA replicons, and the putative prions, [URE3] and [PSI]. review the genetic and biochemical evidence indicating that [URE3] and [PSI] are prion forms of Ure2p and Sup35p, respectively [10].

Chemical compound and disease context of Replicon

• Resolution of this cointegrate is further selected in sucrose growth conditions due to the loss of a conditional suicide marker (the sacB gene of Bacillus subtilis) present in the ColE1 plasmid, leading to unmodified and modified incP/Ad5 replicons that can be differentiated upon restriction analysis [11].
• The shuttle vectors contain portions of plasmid pBR322 required for replication and mobilization, with sites for Anabaena restriction enzymes deleted; cyanobacterial replicon pDU1, which lacks such sites; and determinants for resistance to chloramphenicol, streptomycin, neomycin, and erythromycin [12].
• Twelve-hour exposure of G1 Ehrlich ascites cells to controlled hypoxia (200 ppm of O2 at 1 bar) suppressed replicon initiation [13].
• Ataxia telangiectasia cells displayed normal levels of amsacrine-induced DNA strand breaks during stabilization of cleavable complexes but failed to downregulate replicon initiation after exposure to the topoisomerase inhibitor [14].
• trans-dominant inhibition of poly(ADP-ribosyl)ation sensitizes cells against gamma-irradiation and N-methyl-N'-nitro-N-nitrosoguanidine but does not limit DNA replication of a polyomavirus replicon [15].

Biological context of Replicon

• Plasmids containing transposon derivatives with only one end (either left or right) undergo transposase-dependent transposition between replicons at much lower frequencies, resulting in co-integrate molecules in which there is no substantial duplication of transposon DNA and that appear to be simple fusions of the two plasmids [16].
• This suggests, surprisingly, that initiations of new replicons either may not be inhibited by cycloheximide or, alternatively, that all initiations have already taken place at the very start of S-phase [17].
• Cells in which initiations were not confined to a short interval in the cell cycle (carrying mutations in sequestration or initiation genes or expressing excess initiator protein) could not support stable co-existence of several oriC-dependent replicons [18].
• Here we report that korB in trans expresses incompatibility towards RK2 replicons either when the korB gene dosage is high or when it is expressed from a strong foreign promoter [19].
• Our laboratory has previously demonstrated that high-level HCV replication during acute infection of chimpanzees is associated with the modulation of multiple genes involved in lipid metabolism, and that drugs that regulate cholesterol and fatty acid biosynthesis regulate the replication of the subgenomic HCV replicon in Huh-7 cells [20].

Anatomical context of Replicon

• These unexpected results indicate that, despite its importance, ACE-3 is not essential for low-level amplification and that cis-acting amplification elements are functionally redundant within the autosomal chorion replicon [21].
• We are using the amplified dihydrofolate reductase (DHFR) domain in the methotrexate-resistant CHO cell line, CHOC 400, as a model replicon in which to study this acute radiation effect [22].
• Vaccination with VEE replicon particles expressing E7 (E7-VRP) induced class I-restricted CD8+ T-cell responses as determined by IFN-gamma enzyme-linked immunospot (ELISPOT), tetramer, and cytotoxicity assays [23].
• Logarithmically growing normal fibroblasts displayed D0 values of 6.3 J/m2 and 0.37 microM for the inhibition of DNA synthesis in active replicons by UV and BPDE-I, respectively [24].
• In a subgenomic replicon cell line, 2-C-methyladenosine and 2'-O-methylcytidine inhibit HCV RNA replication [25].

Associations of Replicon with chemical compounds

• RESULTS: The significant effects of cyclosporin A on expression of an HCV replicon and the absence of such effects of FK506, which shares mechanisms of action with cyclosporin A, suggested the involvement of intracellular ligands of cyclosporin A, the cyclophilins [26].
• Two-dimensional gel analysis of Triton-extracted cells show that 20-30% of cyclin remains associated with the replicon clusters [27].
• Our data indicate that the replicons of pGK12 can provide the basis to continue developing efficient genetic systems for B. burgdorferi together with the erythromycin resistance and reporter egfp genes [28].
• In the first step, a cointegrate between the tetracycline-resistant incP/Ad5 replicon and the kanamycin-resistant ColE1-derivative is selected by growing the polA host in the presence of both antibiotics [11].
• In the functional replicon, the dimethyl sulfate and KMnO4 hyperreactive sites appear on complementary strands and are located to one side of an internal palindromic sequence within the LIRs [29].

Gene context of Replicon

• The SKI2 antiviral gene represses the copy numbers of the L-A and L-BC viruses and the 20S RNA replicon, apparently by specifically blocking translation of viral RNA [30].
• Moreover, overexpression of kinase-inactive ATR in U2OS cells severely attenuated UVC-induced Chk1 phosphorylation and reversed the UVC-induced inhibition of replicon initiation, as did overexpression of kinase-inactive Chk1 [31].
• HCV replication was also found to modulate I-TAC expression, with stimulation of Huh-7 cells harboring either the HCV subgenomic or genomic replicon showing significantly increased synergistic effects compared with those previously seen in Huh-7 cells alone with IFN-gamma and TNF-alpha [32].
• It is concluded that, providing nuclear non-S-phase PCNA staining is faint relative to staining of replicon clusters, anti-PCNA antibodies may be excellent markers to detect in situ cells with S-phase DNA contents [33].
• Taken together, these results show that HCV inhibits the expression of GI-GPx in replicon cells to promote its intracellular propagation [34].

Analytical, diagnostic and therapeutic context of Replicon

• Using a selectable subgenomic HCV replicon cell culture system, we have shown that RNAi can specifically inhibit HCV RNA replication and protein expression in Huh-7 cells that stably replicate the HCV genome, and that this antiviral effect is independent of IFN [35].
• Alkaline sedimentation analysis of growing daughter strand DNA, DNA fiber autoradiography, and analysis of the newly formed DNA demonstrated that normal chain growth and DNA maturation (replicon termination) in the initially activated replicons continued in the presence of cycloheximide [13].
• Injection of replicons into established xenograft flank tumors in scid mice resulted in oncolytic activity and extended survival [36].
• These differences in encapsidation, though, were not detected after only two serial passages of the replicons with VV-P1 or upon coinfection and serial passage with type 1 Sabin poliovirus.(ABSTRACT TRUNCATED AT 400 WORDS)[37]
• Surprisingly, the nuclear HBcAg of mutants I97E and I97W, produced from either a replicon or an expression vector, was found to be colocalized with nucleolin and B23 at a frequency of nearly 100% by confocal immunofluorescence microscopy [38].

References