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At least 55 records · Page 3Linked to original sources
PubMed2005

Origins of bidirectional replication of Epstein-Barr virus: models for understanding mammalian origins of DNA synthesis.

Epstein-Barr virus (EBV), provides unique advantages to understand origins of replication in higher eukaryotes. EBV establishes itself efficiently in infected B lymphocytes, where it exists as a 165 kb, circular chromosome which is duplicated once per cell cycle (Adams [1987] J Virol 61:1743-1746). Five to twenty copies of the EBV chromosome are usually present in each cell, increasing the signal/noise ratio for mapping and analyzing its replication origins. Remarkably only one viral protein is required for the synthesis and partitioning of the viral chromosomes: EBV nuclear antigen-1, or EBNA1. EBV uses distinct origins related to the ARS1 origin of Saccharomyces cerevisiae and to that of the dihydrofolate reductase (DHFR) locus in Chinese hamster ovary (CHO) cells [Bogan et al., 2000]. We shall review the properties and the regulation of these two kinds of origins in EBV and relate them to their cellular cousins.

Animals↗
PubMed1983

Possible mechanism for origin of chiral specificity during origins of life.

We have earlier (Origins of Life 10 (1980), 15-30) proposed a conformational theory for the origin of nucleic acid-directed adaptor-mediated ordered and proliferative synthesis of proteins and hence origin of life. Conjunction of L-amino acids and beta-D-ribonucleotides emerges as a natural consequence of a template fitting interaction in this theory of the origin of the genetic decoding apparatus. Here we propose an interesting new concept for the origin of chiral specificity, by showing that two autonomously developing systems of protein-synthesizing machinery, one manufacturing L-peptides (L-system) and the other, D-peptides (D-system) could have arisen and during early stages of evolution L-system could have developed a killer enzyme to destroy the D-system, causing the presently existing chiral specificity in all the evolved organisms on Earth. It would be interesting to look for such 'killer enzymes' in the present-day organisms. Of course, the existence of D-amino acid-containing antibiotics gives some credence to this theory.

Genetic Code↗
PubMed2001

Functional characterization of Marek's disease virus (MDV) origin-binding protein (OBP): analysis of its origin-binding properties.

In previous studies, we identified a Marek's disease virus (MDV) origin-binding protein (OBP) gene that is highly homologous to the herpes simplex virus type 1 UL9 gene that encodes an OBP and functions as an initiator protein for viral DNA replication. In this study, a protein of 95 kDa was produced in coupled in vitro transcription-translation reaction with the plasmid containing the wild type MDV OBP gene. The in vitro synthesized protein was detected by immunoprecipitation with a penta-histidine specific monoclonal antibody. Further characterization of MDV OBP was accomplished using electrophoretic mobility shift assay (EMSA) with the in vitro expressed MDV OBP using a double-stranded (ds) 26-mer oligonucleotide as the probe, which was designed from the putative MDV OBP binding site present in the serotype 1 or 2 MDV replication origin. The EMSA results indicated that MDV OBP could form a protein-DNA complex with the ds 26-mer oligonucleotide designed from serotype 1 or 2 replication origin. A series of 26-mer oligonucleotides with two-base-pair (bp) substitution across the putative MDV OBP binding site were used in competitive EMSA to determine the recognition sequence for the MDV OBP. The results demonstrated that the recognition sequence for MDV OBP was the TTCGCACC that is a subset of a 9-bp element (CGTTCGCAC) conserved in the replication origins of alphaherpesviruses. Furthermore, the results of EMSA with a series of deletion mutants from the N-terminus of MDV OBP indicated that the origin-binding domain was located at the amino acids region 528 to 841 of the wild-type MDV OBP. Taken together, our results suggest that the MDV OBP gene encodes an OBP of MDV.

Amino Acid Sequence↗
PubMed1979

Differences in maternal age-specific rates of Down syndrome between Jews of European origin and of North African or Asian origin.

Rates of Down syndrome in livebirths in West Jerusalem in 1964-1975 were studied in relation to the mother's continent of birth or, if she was born in Israel, to the maternal grandfather's continent of birth. In women of European origin the crude livebirth rate of Down syndrome was 1.3 per 1,000 livebirths. This crude rate and the maternal age-specific rates in this group were very close to those observed in a Swedish study and two studies of white livebirths in the United States. For West Jerusalem women of North African or Asian origin the crude rate was about 2.4 per 1,000 livebirths, and at all maternal ages except the youngest their rates were higher than for women of European origin. The summary adjusted relative risk for a Down syndrome livebirth for all those of North African or Asian origin, compared to those for women of European origin, was about 1.56. If attention is restricted to mothers born outside of Israel, the adjusted relative risk for mothers born in Europe, the Americas or English speaking countries of the British commonwealth compared to those born in North Africa or Asia was 1.97, consistent with a two-fold difference in the likelihood of a Down syndrome livebirth between thes two groups. To our knowledge this is the first report of ethnic differences in maternal age specific rates of Down syndrome that cannot be plausibly explained by differences in ascertainment.

Africa↗
PubMed2005

Origin of French virgin olive oil registered designation of origins predicted by chemometric analysis of synchronous excitation-emission fluorescence spectra.

The authentication of virgin olive oil samples requires usually the use of sophisticated and very expensive analytical techniques, so there is a need for fast and inexpensive analytical techniques for use in a quality control methodology. Virgin olive oils present an intense fluorescence spectra. Synchronous excitation-emission fluorescence spectroscopy (SEEFS) was assessed for origin determination of virgin olive oil samples from five French registered designation of origins (RDOs) (Nyons, Vallée des Baux, Aix-en-Provence, Haute-Provence, and Nice). The spectra present bands between 600 and 700 nm in emission due to chlorophylls a and b and pheophytins a and b. The bands between 275 and 400 nm in emission were attributed to alpha-, beta-, and gamma-tocopherols and to phenolic compounds, which characterize the virgin olive oils compared to other edible oils. The chemometric treatment (PLS1) of synchronous excitation-emission fluorescence spectra allows one to determine the origin of the oils from five French RDOs (Baux, Aix, Haute-Provence, Nice, and Nyons). Results were quite satisfactory, despite the similarity between two denominations of origin (Baux and Aix) that are composed by some common cultivars (Aglandau and Salonenque). The interpretation of the regression coefficients shows that RDOs are correlated to chlorophylls, pheophytins, tocopherols, and phenols compounds, which are different for each origin. SEEFS is part of a global analytic methodology that associates spectroscopic and chromatographic techniques. This approach can be used for traceability and vindicates the RDOs.

Chlorophyll↗
PubMed2003

Perspectives on the origin of microfilaments, microtubules, the relevant chaperonin system and cytoskeletal motors--a commentary on the spirochaete origin of flagella.

The origin of cytoskeleton and the origin of relevant intracellular transportation system are big problems for understanding the emergence of eukaryotic cells. The present article summarized relevant information of evidences and molecular traces on the origin of actin, tubulin, the chaperonin system for folding them, myosins, kinesins, axonemal dyneins and cytoplasmic dyneins. On this basis the authors proposed a series of works, which should be done in the future, and indicated the ways for reaching the targets. These targets are mainly: 1) the reconstruction of evolutionary path from MreB protein of archaeal ancestor of eukaryotic cells to typical actin; 2) the finding of the MreB or MreB-related proteins in crenarchaea and using them to examine J. A. Lake's hypothesis on the origin of eukaryote from "eocytes" (crenarchaea); 3) the examinations of the existence and distribution of cytoskeleton made of MreB-related protein within coccoid archaea, especially in amoeboid archaeon Thermoplasm acidophilum; 4) using Thermoplasma as a model of archaeal ancestor of eukaryotic cells; 5) the searching for the homolog of ancestral dynein in present-day living archaea. During the writing of this article, Margulis' famous spirochaete hypothesis on the origin of flagella and cilia was unexpectedly involved and analyzed from aspects of tubulins, dyneins and spirochaetes. Actually, spirochaete cannot be reasonably assumed as the ectosymbiotic ancestor of eukaryotic flagella and cilia, since their swing depends upon large amount of bacterial flagella beneath the flexible outer wall, but not depends upon their intracellular tubules and the assumed dyneins. In this case, if they had "evolved" into cilia and lost their bacterial flagella, they would immediately become immobile! In fact, tubulin and dynein-like proteins have not been found in any spirochaete.

Actin Cytoskeleton↗
PubMed1997

Unwinding of the box I element of a herpes simplex virus type 1 origin by a complex of the viral origin binding protein, single-strand DNA binding protein, and single-stranded DNA.

The herpes simplex virus type 1 (HSV-1) genome contains three origins of replication: oriL and two copies of oriS. These origins contain specific sequences, box I and box II, linked by an AT-rich segment, that are recognized by an HSV-1-encoded origin binding protein (UL9 protein) which also possesses DNA helicase activity. Despite its intrinsic helicase activity, the UL9 protein is unable to unwind oriS or the box I element of oriS, either in the presence or absence of the HSV-1-encoded single-strand DNA binding protein, ICP8. However, a complex of the UL9 protein and ICP8 can unwind box I if it contains a 3' single-stranded tail at least 18 nt in length positioned downstream of box I. These findings suggest a model for the initiation of HSV-1 DNA replication in which a complex consisting of the UL9 protein bound to box I, and ICP8 bound to single-stranded DNA generated at the A+T rich linker, perhaps as a consequence of transcription, unwinds an HSV-1 origin of replication to provide access to the replication machinery with the consequent initiation of viral DNA replication. This mode of unwinding is distinct from that observed for other animal viruses--e.g., simian virus 40 or bovine papilloma virus--in which the initiator protein, T antigen, or E1 protein alone, unwinds elements of the origin sequence, and the single-strand DNA binding protein serves only to keep the separated strands apart.

DNA, Single-Stranded↗
PubMed2006

The imprinted gene and parent-of-origin effect database now includes parental origin of de novo mutations.

The imprinted gene and parent-of-origin effect database (www.otago.ac.nz/IGC) consists of two sections. One section catalogues the current literature on imprinted genes in humans and animals. The second, and new, section catalogues current reports of parental origin of de novo mutations in humans alone. The addition of a catalogue of de novo mutations that show a parent-of-origin effect expands the scope of the database and provides a useful tool for examining parental origin trends for different types of spontaneous mutations. This new section includes >1700 mutations, found in 59 different disorders. The 85 imprinted genes are described in 152 entries from several mammalian species. In addition, >300 other entries describe a range of reported parent-of-origin effects in animals.

Animals↗
PubMed2006

In vivo transfer of the vanA resistance gene from an Enterococcus faecium isolate of animal origin to an E. faecium isolate of human origin in the intestines of human volunteers.

Transient colonization by vancomycin-resistant enterococci of animal origin has been documented in the intestines of humans. However, little is known about whether transfer of the vanA gene occurs in the human intestine. Six volunteers ingested a vancomycin-resistant Enterococcus faecium isolate of chicken origin, together with a vancomycin-susceptible E. faecium recipient of human origin. Transconjugants were recovered in three of six volunteers. In one volunteer, not only was vancomycin resistance transferred, but also quinupristin-dalfopristin resistance. This study shows that transfer of the vanA gene from an E. faecium isolate of animal origin to an E. faecium isolate of human origin can occur in the intestines of humans. It suggests that transient intestinal colonization by enterococci carrying mobile elements with resistance genes represents a risk for spread of resistance genes to other enterococci that are part of the human indigenous flora, which can be responsible for infections in certain groups of patients, e.g., immunocompromised patients.

Animals↗
PubMed2003

[Difficult diagnosis of fever of unknown origin related to an infraclinic liposarcoma: "small tumor and fever of unknown origin"].

INTRODUCTION: Palpation of soft tissues constitutes part of the physical examination when faced with a patient with fever of unknown origin. Our case highlights the difficulty of diagnosis when the tumor still remains impalpable ten months after onset of fever and severe biological inflammatory process. EXEGESIS: A 49-year-old woman was admitted for fever of unknown origin associated with important biological inflammatory process. In view of her past medical history of breast carcinoma, a search for a relapse was performed and remained negative. Despite multiple investigations and repeated physical examinations, no diagnosis was obtained. Finally, [18F] fluorodoexyglucose positron emission tomography led to a diagnosis showing a high fixation located in the right thigh, related to a myxoid liposarcoma after surgical resection. CONCLUSION: Dramatic regression of fever and biological inflammatory process after surgical treatment illustrates the concept of "small tumor and fever of unknown origin", an exceptional entity but which physicians should be aware of. The role of new technical imaging with [18F] fluorodoexyglucose positron emission tomography has however to be clarified in the evaluation of fever of unknown origin.

Breast Neoplasms↗
PubMed2001

Replication of a chimeric origin containing elements from Epstein-Barr virus ori P and bovine papillomavirus minimal origin.

The bovine papillomavirus E2 protein is a multifunctional protein that activates viral transcription, co-operates in initiation of viral DNA replication, and is required for long-term episomal maintenance of viral genomes. The EBNA1 protein of Epstein-Barr virus is required for synthesis and maintenance of Epstein-Barr virus genomes. Both viral proteins act through direct interactions with their respective DNA sequences in their origins of replication. The chimeric protein E2:EBNA1, which consists of an transactivation domain of E2 and DNA binding domain of EBNA1 supported the replication of the chimeric origin that contained EBNA1 binding sites in place of the E2 binding sites principally as full-length E2 did in the case of papillomavirus minimal origin. This indicates that the chimeric protein E2:EBNA1 is competent to assemble a replication complex similar to the E2 protein. These data confirm the earlier observations that the only part of E2 specifically required for its activity in replication is the N-terminal activation domain and the function of the DNA binding domain of E2 in the initiation of replication is to tether the transactivation domain of E2 to the origin of replication.

Binding Sites↗
PubMed2003

Kaposi's sarcoma-associated herpesvirus lytic origin (ori-Lyt)-dependent DNA replication: identification of the ori-Lyt and association of K8 bZip protein with the origin.

Herpesviruses utilize different origins of replication during lytic versus latent infection. Latent DNA replication depends on host cellular DNA replication machinery, whereas lytic cycle DNA replication requires virally encoded replication proteins. In lytic DNA replication, the lytic origin (ori-Lyt) is bound by a virus-specified origin binding protein (OBP) that recruits the core replication machinery. In this report, we demonstrated that DNA sequences in two noncoding regions of the Kaposi's sarcoma-associated herpesvirus (KSHV) genome, between open reading frames (ORFs) K4.2 and K5 and between K12 and ORF71, are able to serve as origins for lytic cycle-specific DNA replication. The two ori-Lyt domains share an almost identical 1,153-bp sequence and a 600-bp downstream GC-rich repeat sequence, and the 1.7-kb DNA sequences are sufficient to act as a cis signal for replication. We also showed that an AT-palindromic sequence in the ori-Lyt domain is essential for the DNA replication. In addition, a virally encoded bZip protein, namely K8, was found to bind to a DNA sequence within the ori-Lyt by using a DNA binding site selection assay. The binding of K8 to this region was confirmed in cells by using a chromatin immunoprecipitation method. Further analysis revealed that K8 binds to an extended region, and the entire region is 100% conserved between two KSHV ori-Lyt's. K8 protein displays significant similarity to the Zta protein of Epstein-Barr virus (EBV), which is a known OBP of EBV. This notion, together with the ability of K8 to bind to the KSHV ori-Lyt, suggests that K8 may function as an OBP in KSHV.

Base Sequence↗
PubMed1991

Two potential Petunia hybrida mitochondrial DNA replication origins show structural and in vitro functional homology with the animal mitochondrial DNA heavy and light strand replication origins.

Four Petunia hybrida mitochondrial (mt) DNA fragments have been isolated, sequenced, localized on the physical map and analyzed for their ability to initiate specific DNA synthesis. When all four mtDNA fragments were tested as templates in an in vitro DNA synthesizing lysate system, developed from purified P. hybrida mitochondria, specific initiation of DNA synthesis could only be observed starting within two fragments, oriA and oriB. When DNA synthesis incubations were performed with DNA templates consisting of both the A and B origins in the same plasmid in complementary strands, DNA synthesis first initiates in the A-origin, proceeds in the direction of the B-origin after which replication is also initiated in the B-origin. Based on these observations, a replication model for the P. hybrida mitochondrial genome is presented.

Animals↗
PubMed1983

Effect of a stem-loop structure within the SV40 replication origin upon SV40 T antigen binding to origin region sequences.

Heteroduplexes were formed between SV40 replication origin-containing DNA fragments derived from wild-type genomic DNA and a viral deletion mutant (dl295) lacking 18 base pairs from a 27 bp inverted repeat that is imbedded within the minimal replication origin sequence. Among these structures were molecules bearing a 7 bp stem and a 3 nucleotide loop on the wild-type strand between nucleotides 5230 and 6. By nondenaturing gel electrophoresis, heteroduplex molecules bearing such a structure on the E-strand could be separated from those with the complementary structure on the L-strand, and either heteroduplex could be so separated from either the wild-type or dl295 homoduplex fragment. Each of these forms was singly 5' or 3' end-labeled and then evaluated as a target for specific binding to purified SV40 large T antigen isolated from wild-type virus-infected cells. The results of DNAase footprint protection analyses showed that the existence of both the E- and L-strand stem-loop structures inhibited T binding to site 2 which composes much of the minimal origin sequence. By contrast, T bound readily to this site in both homoduplexes. Furthermore, T protected both E- and L-strand sequences of its strongest binding site (site 1)--which abuts the early side of site 2--when the site 2 stem-loop was on the L-strand, and protected L-strand site 1 sequences normally when the stem-loop was on the E-strand. However, a marked alteration of binding to site 1 E-strand sequences was noted when the stem-loop was on the E-strand. Thus this alteration in replication origin secondary structure resulted in discrete local and vicinal effects on T binding. Furthermore, the results suggest that within site 1--a sequence employed as an early transcriptional regulatory locus--T antigen can bind specifically and tightly to one strand without exhibiting similar behavior on the other strand.

Antigens, Viral, Tumor↗
PubMed1984

Dual-origin plasmid vectors whose origin of replication is controlled by the coliphage lambda promoter pL.

The insertion of an XhoI linker 30 bp from the 5' end of the RNA II primer for ColE1 plasmid replication has allowed us to replace the natural RNA II promoter by other controllable promoters, in particular lambda pL. Manipulation of this modified origin was facilitated by constructing dual-origin plasmids, stable maintenance being directed by the pSC101 origin. Experiments showed that such dual-origin plasmids could be stably maintained at approximately four copies per chromosome at 30 degrees C and readily amplified by thermal induction of strains carrying a thermolabile lambda repressor. The use of such plasmids for the construction of stable, amplifiable expression vectors is discussed.

Bacteriocin Plasmids↗
PubMed2004

The origin of the tRNA molecule: implications for the origin of protein synthesis.

A model for tRNA molecule origin is discussed. The model postulates that this molecule originated simply by direct duplication (and subsequent evolution) of a gene coding for an RNA hairpin structure, which can thus be hypothesized as the evolutionary precursor of the tRNA molecule. The main properties are defined for these hairpin structures and it is suggested that these structures might have housed, near their 3' end, anticodons that were transferred to the loop of the tRNA anticodon during duplication of the hairpin structures. Moreover, the main characteristics are given for the evolutionary intermediary formed by direct duplication of the hairpin structure, i.e. the double hairpin. The evolutionary stages envisaged by this model for tRNA origin seem to naturally imply some evolutionary transitions through which the origin of protein synthesis passed. Finally, some strong historical evidence is provided to corroborate the model.

Animals↗
PubMed2002

Artificial mimicking of physiological active transport by a membrane co-cultured with two different cells: hepatic origin HepG2 and renal origin PCTL-MDR.

We designed a membrane culture unit on which 2 different cell lines were co-cultured to achieve selective and active transport of toxins. Hepatic origin HepG2 and renal origin multidrug-resistant gene-transduced proximal convoluted tubular cell line (PCTL-MDR) were cultured on the opposite sides of an expanded polytetrafluoroethylene membrane. The activity of testosterone hydroxylation by original HepG2 was very low; however, the cytochrome p450 (CYP) 3A4-transduced recombinant HepG2 metabolized the substrate efficiently. Testosterone added into the outer medium was hydrolyzed by HepG2, and the metabolites were preferentially transported to the inner medium by PCTL-MDR. [3H]-digoxin and [14C]-inulin were added to the outer medium; the digoxin was transported from the outer to inner space through the cell monolayer but the inulin was not, suggesting that the membrane actively transported only the substrate of the channel protein, MDR. The cells were irradiated (10 Gy) to prevent a membrane leak due to overgrowth. The irradiation did not induce apoptosis but resulted in long-lasting membrane function without leakage. The membrane co-cultured with hepatic and renal origin cells will enable a novel hemofiltration system with selective and active transport activities.

Animals↗
PubMed1988

Interaction of origin binding protein with an origin of replication of herpes simplex virus 1.

Herpes simplex virus 1 encodes a protein that binds specifically to a viral DNA replication origin (oriS). This origin-binding protein has been purified to homogeneity by means of sequence-specific DNA affinity chromatography. The purified origin-binding protein, which has a molecular weight of 83,000, interacts with both parts of the oriS dyad; however, the affinity for the two sites differs by an order of magnitude. The sequence TTCGCA occurs as a nearly perfect direct repeat within the two sites and may constitute the recognition sequence for the origin-binding protein.

Base Sequence↗