Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Origin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed1997

Replication of simian virus 40 origin-containing DNA during infection with a recombinant Autographa californica multiple nuclear polyhedrosis virus expressing large T antigen.

Autographica californica multiple nuclear polyhedrosis virus (AcMNPV) has been shown to encode many of the enzymes involved in the replication of its own DNA. Although the AcMNPV genome contains multiple sets of reiterated sequences that are thought to function as origins of DNA replication, no initiator protein has yet been identified in the set of viral replication enzymes. In this study, the ability of a heterologous origin initiator system to promote DNA replication in AcMNPV-infected cells was examined. A recombinant AcMNPV that expressed the simian virus 40 (SV40) large T antigen was surprisingly found to induce the efficient replication of a transfected plasmid containing an SV40 origin. This replication was subsequently found to involve three essential components: (i) T antigen, since replication of SV40 origin-containing plasmids was not induced by wild-type AcMNPV which did not express this protein; (ii) an intact SV40 core origin, since deletion of specific functional motifs within the origin resulted in a loss of replicative abilities; and (iii) one or more AcMNPV-encoded proteins, since viral superinfection was required for plasmid amplification. Characterization of the replicated DNA revealed that it existed as a high-molecular-weight concatemer and underwent significant levels of homologous recombination between inverted repeat sequences. These properties were consistent with an AcMNPV-directed mode of DNA synthesis rather than that of SV40 and suggested that T antigen-SV40 origin complexes may be capable of initiating DNA replication reactions that can be completed by AcMNPV-encoded enzymes.

Animals↗
PubMed2004

Interactions required for binding of simian virus 40 T antigen to the viral origin and molecular modeling of initial assembly events.

The purified T-antigen origin binding domain binds site specifically to site II, the central region of the simian virus 40 core origin. However, in the context of full-length T antigen, the origin binding domain interacts poorly with DNA molecules containing just site II. Here we investigate the contributions of additional core origin regions, termed the flanking sequences, to origin recognition and the assembly of T-antigen hexamers and double hexamers. Results from these studies indicate that in addition to site-specific binding of the T-antigen origin binding domain to site II, T-antigen assembly requires non-sequence-specific interactions between a basic finger in the helicase domain and particular flanking sequences. Related studies demonstrate that the assembly of individual hexamers is coupled to the distortions in the proximal flanking sequence. In addition, the point in the double-hexamer assembly process that is regulated by phosphorylation of threonine 124, the sole posttranslational modification required for initiation of DNA replication, was further analyzed. Finally, T-antigen structural information is used to model various stages of T-antigen assembly on the core origin and the regulation of this process.

Animals↗
PubMed1998

Multiple orientation-dependent, synergistically interacting, similar domains in the ribosomal DNA replication origin of the fission yeast, Schizosaccharomyces pombe.

Previous investigations have shown that the fission yeast, Schizosaccharomyces pombe, has DNA replication origins (500 to 1500 bp) that are larger than those in the budding yeast, Saccharomyces cerevisiae (100 to 150 bp). Deletion and linker substitution analyses of two fission yeast origins revealed that they contain multiple important regions with AT-rich asymmetric (abundant A residues in one strand and T residues in the complementary strand) sequence motifs. In this work we present the characterization of a third fission yeast replication origin, ars3001, which is relatively small ( approximately 570 bp) and responsible for replication of ribosomal DNA. Like previously studied fission yeast origins, ars3001 contains multiple important regions. The three most important of these regions resemble each other in several ways: each region is essential for origin function and is at least partially orientation dependent, each region contains similar clusters of A+T-rich asymmetric sequences, and the regions can partially substitute for each other. These observations suggest that ars3001 function requires synergistic interactions between domains binding similar proteins. It is likely that this requirement extends to other fission yeast origins, explaining why such origins are larger than those of budding yeast.

Base Sequence↗
PubMed2001

Reconstitution of licensed replication origins on Xenopus sperm nuclei using purified proteins.

BACKGROUND: In order to ensure precise chromosome duplication, eukaryotes "license" their replication origins during late mitosis and early G1 by assembling complexes of Mcm2-7 onto them. Mcm2-7 are essential for DNA replication, but are displaced from origins as they initiate, thus ensuring that no origin fires more than once in a single cell cycle. RESULTS: Here we show that a combination of purified nucleoplasmin, the origin recognition complex (ORC), Cdc6, RLF-B/Cdt1 and Mcm2-7 can promote functional origin licensing and the assembly of Mcm2-7 onto Xenopus sperm nuclei. The reconstituted reaction is inhibited by geminin, a specific RLF-B/Cdt1 inhibitor. Interestingly, the purified ORC used in the reconstitution had apparently lost the Orc6 subunit, suggesting that Orc6 is not essential for replication licensing. We use the reconstituted system to make a preliminary analysis of the different events occurring during origin assembly, and examine their nucleotide requirements. We show that the loading of Xenopus ORC onto chromatin is strongly stimulated by both ADP, ATP and ATP-gamma-S whilst the loading of Cdc6 and Cdt1 is stimulated only by ATP or ATP-gamma-S. CONCLUSIONS: Nucleoplasmin, ORC, Cdc6, RLF-B/Cdt1 and Mcm2-7 are the only proteins required for functional licensing and the loading of Mcm2-7 onto chromatin. The requirement for nucleoplasmin probably only reflects a requirement to decondense sperm chromatin before ORC can bind to it. Use of this reconstituted system should allow a full biochemical analysis of origin licensing and Mcm2-7 loading.

Animals↗
PubMed2005

Epigenetic control of replication origins.

Efficient duplication of the eukaryotic genome requires the spatial and temporal coordination of numerous replication origins on each chromosome. Epigenetic factors, like chromatin environment, can have profound effects on origin site selection, utilization frequency, and cell cycle firing time. Precisely how chromatin contributes to origin site selection and timing is not completely understood. Recently, we reported on the cell cycle changes in chromatin structure at the plasmid replication origins of Epstein-Barr Virus (EBV) and Kaposi's Sarcoma-Associated Herpes virus (KSHV). These studies and others suggest that cell cycle changes in histone modification and nucleosome remodeling regulate prereplication factor assembly and initiation of DNA replication at origins. We discuss how these studies of viral origins may provide important insights into epigenetic control of cellular chromosome origins.

Epigenesis, Genetic↗
PubMed1999

Elevated maternal age-specific rates of Down syndrome liveborn offspring of women of Mexican and Central American origin in California.

BACKGROUND: Maternal age-specific rates of Down syndrome livebirths are widely utilized in personal and policy decisions concerning provision of and election of prenatal cytogenetic diagnostic services. The only extensive reference data available are on those of primarily European ancestral origin. In the absence of definitive evidence of any ethnic, racial or environmental influence upon rates (other than those associated with age) these rate schedules have been widely applied to those of all national origins. METHODS: Available material age-specific data on livebirths from intensive studies on those of Hispanic (primarily of Mexican and Central American background) and of other origin in populations in the U.S.A. with likely complete ascertainment were analysed. The numbers observed were compared with (i) those predicted from established published rate schedules in those of primarily European origin, and (ii) with the observations on livebirths of non-Hispanic European origin in the same population as the Hispanic live births. RESULTS: In comparisons with the numbers predicted from published rates, observed numbers of case among Hispanic live births were increased by 19 per cent (SE 0.06) in younger mothers, 23 per cent in older mothers (SE 0.07) and 20 per cent (SE 0.04) in those of all ages. Comparisons with observed rates in those of Hispanic origin with those observed in non-Hispanic births in the same time intervals and populations indicated that the excess rates in Hispanics were not attributable to some local factor increasing rates in all ethnic groups at least among those under 35. CONCLUSIONS: Data on mothers of Mexican and Central American origin residing in the U.S.A. indicate maternal age-specific rates of Down syndrome in live births about 20 per cent greater than those in published rate schedules on Down syndrome, widely used in decisions concerning election or provison of prenatal diagnostic services. The reason for this difference remains unknown.

Adolescent↗
PubMed2000

Origin of uniparental disomy 15 in patients with Prader-Willi or Angelman syndrome.

Maternal uniparental disomy (UPD) accounts for approximately 25% of Prader-Willi patients (PWS) and paternal UPD for about 2-5% of Angelman syndrome (AS) patients. These findings and the parental origin of deletions are evidence of genomic imprinting in the cause of PWS and AS. The natural occurrence of UPD individuals allows the study of meiotic mechanisms resulting in chromosomal nondisjunction (ND). We selected patients with UPD15 from our sample of 30 PWS and 40 AS patients to study the origin of ND and the recombination along chromosome 15. These patients were analyzed with 10 microsatellites throughout the entire chromosome 15 (D15S541, D15S542, D15S11, D15S113, GABRB3, CYP19, D15S117, D15S131, D15S984, D15S115). The analysis disclosed seven heterodisomic PWS cases originating by meiosis I (MI) ND (four showed recombination and three no recombination), and one isodisomic PWS UPD15 originating by postzygotic duplication. Among the five paternal UPD15, we detected four isodisomies, three of which showed homozigosity for all markers, corresponding to a mitotic error, and one case originating from a paternal MII ND. Our results indicate that besides maternal MI and MII ND, paternal ND occurs when a PWS UPD15 patient originates from mitotic duplication of the maternal chromosome 15. ND events in AS are mainly due to mitotic errors, but paternal MII ND can occur and give origin to an AS UPD15 individual by two different mechanisms: rescue of a trisomic fetus or fertilization of a nullisomic egg with the disomic sperm, and in this case paternal and maternal ND are necessary.

Adult↗
PubMed2000

Genetic alterations in gastric cancer cell lines and their original tissues.

To investigate the genetic changes that occur during establishment of gastric cancer cell lines, 4 gastric cancer cell lines and their original tumor tissues were examined for microsatellite instability (MSI), loss of heterozygosity (LOH), and p53 mutation. MSI status did not change during the establishment, though the cell lines gained frameshift mutation in some of the genes with polytract coding sequences. There was no difference in p53 mutation between the cell lines and the original tumors. The frequency of LOH was similar between the cell lines and each original tumor, in the range 30.8% to 85.7%. The difference in the LOH results between the cell lines and the original tumors was not greater than the difference between the different areas of the original tumors. The above results suggested that most of the genetic alterations, such as MSI, LOH, and p53 gene mutation, were sustained during the establishment of gastric cancer cell lines. Minor genetic differences between original tumor tissues and cancer cell lines could be explained as a tumor heterogeneity because separate areas of the original tumor tissues manifest similar variations.

Frameshift Mutation↗
PubMed2005

Deep time and the search for anthropoid origins.

Recent fossil discoveries, phylogenetic analyses, revised reconstructions of continental drift, and accumulating molecular evidence have all yielded new information relating to anthropoid origins within the broader context of primate evolution. There is an emerging consensus among molecular studies that four superorders of eutherian mammals can be recognized: Afrotheria, Euarchontoglires (to which primates belong), Laurasiatheria, and Xenarthra. Overall, molecular phylogenies for mammals agree with some statistical analyses of the primate fossil record in indicating an early origin for primates around 85 Ma ago, and the divergence of haplorhines and strepsirrhines at ca. 77 Ma. Such an ancient date for the origin of haplorhines is some 17 Ma prior to the first known possible primate, and some 22 Ma before the earliest fossil evidence of undoubted euprimates. Because anthropoid fossils date back at least to the late Eocene and perhaps to the middle Eocene, and given indications of an early origin for primates, it is unlikely that ancestral anthropoids arose within any other currently known clade of fossil primates (adapiforms, omomyiforms, strepsirrhines, or tarsiiforms). Implications of new molecular, morphological, and biogeographic lines of evidence are explored with respect to the likely time and place of the origin of anthropoids. Four competing, testable hypotheses are reviewed in detail: 1) the Paratethyan hypothesis, 2) the continental Asian hypothesis, 3) the Indo-Madagascar hypothesis, and 4) the African hypothesis. A case is made that current evidence best supports a relatively ancient Gondwanan origin for primates, as well as a Gondwanan (African or Indo-Madagascan) origin for anthropoids at least as old as that of any other currently documented major primate clade. Available fossil evidence at present seems to be most compatible with the African hypothesis, but it is noteworthy that primates are included not in Afrotheria but in Euarchontoglires.

Animals↗
PubMed1991

Mapping replication origins in yeast chromosomes.

The replicon hypothesis, first proposed in 1963 by Jacob and Brenner, states that DNA replication is controlled at sites called origins. Replication origins have been well studied in prokaryotes. However, the study of eukaryotic chromosomal origins has lagged behind, because until recently there has been no method for reliably determining the identity and location of origins from eukaryotic chromosomes. Here, we review a technique we developed with the yeast Saccharomyces cerevisiae that allows both the mapping of replication origins and an assessment of their activity. Two-dimensional agarose gel electrophoresis and Southern hybridization with total genomic DNA are used to determine whether a particular restriction fragment acquires the branched structure diagnostic of replication initiation. The technique has been used to localize origins in yeast chromosomes and assess their initiation efficiency. In some cases, origin activation is dependent upon the surrounding context. The technique is also being applied to a variety of eukaryotic organisms.

Blotting, Southern↗
PubMed2004

Development of the nervus terminalis: origin and migration.

The origin of the nervus terminalis is one of the least well understood developmental events involved in generating the cranial ganglia of the forebrain in vertebrate animals. This cranial nerve forms at the formidable interface of the anteriormost limits of migrating cranial neural crest cells, the terminal end of the neural tube and the differentiating olfactory and adenohypophyseal placodes. The complex cellular interactions that give rise to the various structures associated with the sensory placode (olfactory) and endocrine placode (adenohypophysis) surround and engulf this enigmatic cranial nerve. The tortured history of nervus terminalis development (see von Bartheld, this issue, pages 13-24) reflects the lack of consensus on the origin (or origins), as well as the experimental difficulties in uncovering the origin, of the nervus terminalis. Recent technical advances have allowed us to make headway in understanding the origin(s) of this nerve. The emergence of the externally fertilized zebrafish embryo as a model system for developmental biology and genetics has shed new light on this century-old problem. Coupled with new developmental models are techniques that allow us to trace lineage, visualize gene expression, and genetically ablate cells, adding to our experimental tools with which to follow up on studies provided by our scientific predecessors. Through these techniques, a picture is emerging in which the origin of at least a subset of the nervus terminalis cells lies in the cranial neural crest. In this review, the data surrounding this finding will be discussed in light of recent findings on neural crest and placode origins.

Animals↗
PubMed1996

The independent variable in the early origin of higher taxa.

Taxa of high rank tend to originate at earlier times in the fossil record than do taxa of lower rank. Statistical analysis of published stratigraphic ranges shows that the early origin of higher taxa is a secondary consequence of taxonomic structure. For instance, the probability that the origination of an order also begins a new class is a decreasing function of the number of orders that have already originated in the same phylum. Similar decreasing functions also apply to families and orders within classes, and to genera and families within orders, indicating that the pattern of origination is self-similar across at least three taxonomic ranks. These functions are sufficient to predict the extent to which higher taxa originate earlier, but the converse is not true. These results are more consistent with genetic constraints or taxonomic hindsight than with ecological saturation as explanations for the early origin of higher taxa.

Animals↗
PubMed1993

Inhibition of herpes simplex virus type 1 DNA replication by mutant forms of the origin-binding protein.

The herpes simplex virus type 1 (HSV-1) origin-binding protein (OBP) is a sequence-specific DNA binding protein encoded by gene UL9 which interacts with the viral origins of DNA replication and also exhibits DNA helicase activity. Sequence-specific DNA binding activity has previously been shown to reside within the C-terminal 317 amino acids, and when expressed alone, this domain exerts a dominant inhibitory effect on HSV-1 DNA synthesis. We have tested several UL9 gene mutants for ability to support or interfere with viral DNA replication. Mutants affected in an ATP binding motif presumed to be associated with DNA helicase activity (ATP-), or defective in origin binding (OBP-) were unable to support replication in a transient assay for HSV-1 origin-dependent DNA synthesis. When the products were screened for their ability to interfere with replication, the ATP- but not the OBP- mutant was inhibitory. Introduction of a mutation which abolished origin-binding activity into the isolated C-terminal fragment also removed the ability to interfere. The C-terminal fragment retained inhibitory activity when the wild-type (wt) protein was specified by a plasmid in which an OBP recognition site within the UL9 gene coding region had been mutated so as to prevent binding without affecting the encoded amino acids. These results suggest that in this assay inhibition of DNA synthesis probably results primarily from competition between mutant and wt forms of OBP for binding to the viral replication origins. The infectivity of HSV-1 DNA in co-transfection experiments was greatly reduced by mutant UL9 proteins which interfered with origin-dependent DNA replication and also by high level expression of the wt polypeptide.

Animals↗
PubMed1984

Origins of replication and gene regulation.

Eukaryotic chromosomes appear to consist of many replicons, the time of replication of which is probably controlled by specific origins. However, plasmids without specific eukaryotic origins may also replicate in some cells when injected into nuclei or transferred during transformation. The efficiency and the mechanisms of their initiation are still uncertain. A number of reports are cited which indicate that natural eukaryotic DNAs initiate their replication from specific origins. The nature of these origins are known in only a few instances and no general conclusions can yet be given about the nucleotide sequences involved. Short dispersed repeats of the Alu type appear to function as origins since they enhance the efficiency of replication of vector plasmids in Xenopus eggs. Certain sequences from a variety of eukaryotic DNAs also enhance the replicative potential of plasmids in yeast cells. The common features of such initiators or enhancers is uncertain. If dispersed repeats are origins in mammalian chromosomes, the number appears to be excessive. Either only a subset are functional, or the functional ones are only suborigins in larger replicons in which master origins (not yet isolated) function in the regulation of the timing of replication. Evidence is cited which indicates that the regulation of the time of replication of a gene or gene cluster is part of a regulatory system that makes the DNA available for transcription or leaves it in an inactive state. About one-half the DNA in mammalian cells is replicated in the first half of S phase (SE). After a brief pause in mid-S phase, the remainder of the DNA is replicated in what is designated late S (SL). The fractions replicated in SE and SL may vary in other phylogenetic groups, but wherever division of differentiated cells occurs such fractions are likely to be found. The following hypothesis is proposed. The DNA replicated in SL is suppressed in transcription, if it has the appropriate promoter regions, because the newly replicated DNA is complexed with proteins that suppress transcription. These proteins are only available during SL. Those genes replicated in SE are complexed with a different set of proteins which leave the promoter regions open for transcription when the appropriate regulatory molecules are available. In this way an inactive state or potentially active state can be transmitted from one cell generation to the next. Evidence is cited which indicates that genes which are active in all cells at some stage in the cell cycle are replicated in SE.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Origin of replication of Escherichia coli plasmid RSF 1030.

The nucleotide sequence of a region of plasmid RSF 1030 that includes the origin of DNA replication was determined using the DNA of a small derivative, pST19. The nucleotide sequence of the pST 19 origin region is very similar to that of the ColE1 origin except for a 25 base pair (bp) deletion about 350 bp upstream of the origin and a considerable difference in the region between 400 and 600 bp upstream of the origin. Replication of pST19 starts at one of three consecutive nucleotides (dA, dA or dC) located at a unique position in the region where the nucleotide sequence is identical to that of the ColE1 origin. There are two major sites of initiation of transcription in the region. Transcription from one of the sites yields the primer precursor that can be cleaved by RNase H to form the primer of about 530 nucleotides long. Transcription from the other site proceeds on the opposite strand and terminates close to the primer initiation site to yield species I RNA (or RNA I) about 105 nucleotides long. The presumed RNA polymerase binding sites in the promoters of these transcripts differ from those of the corresponding ColE1 transcripts. Incompatibility specified by pST19 is different from that specified by ColE1. Hypothetical peptides encoded by the origin region of these plasmids are unlikely to be involved in the determination of incompatibility. It has been shown that RNA I is an incompatibility-group specific inhibitor of primer formation. Despite a significant difference in nucleotide sequence, the primer RNA and RNA I of pST19 can be folded into structures analogous to those of the ColE1 transcripts.

Base Sequence↗
PubMed1989

Specificity of the interactions between the Rep proteins and the origins of replication of Staphylococcus aureus plasmids pT181 and pC221.

pT181 and pC221 are closely related Staphylococcus aureus plasmids with the same genome organization, which is characterized by the overlapping of the origin of replication with the sequence encoding a protein, Rep, essential for plasmid replication. Former results have shown the lack of in vivo cross-complementation between these two plasmids, while in vitro studies have revealed the ability of both Rep proteins to act on either origin. One possible explanation for this difference was based on a previous analysis of the incompatibility expressed by the origin of replication of these plasmids, showing that the origin embedded in the rep gene competes for Rep utilization with the origin of a test plasmid and that changes in the sequence of the origin reduce its ability to compete. To avoid this problem, in the present work special hybrids were constructed in which the origin of replication overlapping the rep gene was mutationally inactivated, without changing the amino acid sequence of the encoded protein. The level of Rep expression by these hybrids could be varied by taking advantage of what is presently known about the control of Rep synthesis in plasmid pT181.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗
PubMed2004

Accuracy of CT angiography in the assessment of a fetal origin of the posterior cerebral artery.

An uncommon cause of cerebral ischemia in the territory of the posterior cerebral artery (PCA) is the combination of a fetal origin of the PCA and atherosclerotic disease in the internal carotid artery. This study compared the accuracy of CTA with DSA in the assessment of a fetal origin of the PCA. Patients in whom an intracranial DSA and CTA had been performed were reviewed. A fetal origin was defined as a normal-sized patent posterior communicating artery (PCoA) with hypoplasia or aplasia of the ipsilateral P1 segment. One hundred PCAs in 51 patients were analyzed. A fetal origin was present in ten vessels (10%, eight patients). CTA revealed all of them. CTA considered an additional three vessels as having a fetal origin, while DSA revealed a PCoA with the same diameter as the P1 segment of the PCA. Sensitivity and specificity of CTA in the assessment of a fetal origin could be estimated at 100 and 97%, respectively. Positive and negative predictive values were 77 and 100%, respectively. CTA can be considered a valid diagnostic tool for the assessment of a fetal origin of the PCA in patients with a cerebral ischemic event in the territory of the PCA.

Adult↗
PubMed1983

Relation between site of origin of ventricular tachycardia and relative left ventricular myocardial perfusion and wall motion.

To assess the relation between the site of origin of ventricular tachycardia (VT) and relative myocardial perfusion and wall motion, 18 patients with a history of recurrent sustained VT underwent cardiac catheterization, invasive electrophysiologic study with endocardial mapping, and resting radionuclide ventriculography. In addition, 6 patients had exercise and redistribution thallium-201 scintigraphy, whereas the remaining 12 patients had resting thallium scans. The site of origin of VT (determined by catheter and intraoperative endocardial mapping) was correlated with relative myocardial perfusion (thallium) and left ventricular (LV) wall motion. All patients had significant (greater than 50% narrowing) coronary artery disease and 16 had LV aneurysms. Twenty sites of origin of VT (28 morphologies) were identified in these 18 patients. Of the 9 patients with multiple VT morphologies, the VT originated at disparate sites in 2 patients. All 18 patients had thallium defects at rest and 3 patients had additional reversible (ischemic) defects on exercise. Of the 20 sites of origin of VT, 16 were at the periphery of the thallium defect, 1 was adjacent to it, and 3 were in the center of it. In the 16 patients with LV aneurysm, there were 18 sites of origin: 15 at the border of the aneurysm, 1 adjacent to it, and 2 within it. The data suggest that in patients with VT and coronary artery disease the site of origin is usually the periphery of a resting thallium defect, and in patients with LV aneurysm the site is the border of the aneurysm.

Adult↗