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 865 records · Page 48Linked to original sources
PubMed2001

UvsW protein regulates bacteriophage T4 origin-dependent replication by unwinding R-loops.

The UvsW protein of bacteriophage T4 is involved in many aspects of phage DNA metabolism, including repair, recombination, and recombination-dependent replication. UvsW has also been implicated in the repression of origin-dependent replication at late times of infection, when UvsW is normally synthesized. Two well-characterized T4 origins, ori(uvsY) and ori(34), are believed to initiate replication through an R-loop mechanism. Here we provide both in vivo and in vitro evidence that UvsW is an RNA-DNA helicase that catalyzes the dissociation of RNA from origin R-loops. Two-dimensional gel analyses show that the replicative intermediates formed at ori(uvsY) persist longer in a uvsW mutant infection than in a wild-type infection. In addition, the inappropriate early expression of UvsW protein results in the loss of these replicative intermediates. Using a synthetic origin R-loop, we also demonstrate that purified UvsW functions as a helicase that efficiently dissociates RNA from R-loops. These and previous results from a number of studies provide strong evidence that UvsW is a molecular switch that allows T4 replication to progress from a mode that initiates from R-loops at origins to a mode that initiates from D-loops formed by recombination proteins.

Bacteriophage T4↗
PubMed2006

The Chinese hamster dihydrofolate reductase replication origin decision point follows activation of transcription and suppresses initiation of replication within transcription units.

Chinese hamster ovary (CHO) cells select specific replication origin sites within the dihydrofolate reductase (DHFR) locus at a discrete point during G1 phase, the origin decision point (ODP). Origin selection is sensitive to transcription but not protein synthesis inhibitors, implicating a pretranslational role for transcription in origin specification. We have constructed a DNA array covering 121 kb surrounding the DHFR locus, to comprehensively investigate replication initiation and transcription in this region. When nuclei isolated within the first 3 h of G1 phase were stimulated to initiate replication in Xenopus egg extracts, replication initiated without any detectable preference for specific sites. At the ODP, initiation became suppressed from within the Msh3, DHFR, and 2BE2121 transcription units. Active transcription was mostly confined to these transcription units, and inhibition of transcription by alpha-amanitin resulted in the initiation of replication within transcription units, indicating that transcription is necessary to limit initiation events to the intergenic region. However, the resumption of DHFR transcription after mitosis took place prior to the ODP and so is not on its own sufficient to suppress initiation of replication. Together, these results demonstrate a remarkable flexibility in sequence selection for initiating replication and implicate transcription as one important component of origin specification at the ODP.

Animals↗
PubMed2006

Essential elements of a licensed, mammalian plasmid origin of DNA synthesis.

We developed a mammalian plasmid replicon with a formerly uncharacterized origin of DNA synthesis, 8xRep*. 8xRep* functions efficiently to support once-per-cell-cycle synthesis of plasmid DNA which initiates within Rep*. By characterizing Rep*'s requirements for acting as an origin, we have uncovered several striking properties it shares with DS, the only other well-characterized, licensed, mammalian plasmid origin of DNA synthesis. Rep* contains a pair of previously unrecognized Epstein-Barr nuclear antigen 1 (EBNA1)-binding sites that are both necessary and sufficient in cis for its origin activity. These sites have an essential 21-bp center-to-center spacing, are bent by EBNA1, and recruit the origin recognition complex. The properties shared between DS and Rep* define cis and trans characteristics of a mammalian, extrachromosomal replicon. The role of EBNA1 likely reflects its evolution from cellular factors involved in the assembly of the initiation machinery.

Base Sequence↗
PubMed2000

Evidence for symmetric chromosomal inversions around the replication origin in bacteria.

BACKGROUND: Whole-genome comparisons can provide great insight into many aspects of biology. Until recently, however, comparisons were mainly possible only between distantly related species. Complete genome sequences are now becoming available from multiple sets of closely related strains or species. RESULTS: By comparing the recently completed genome sequences of Vibrio cholerae, Streptococcus pneumoniae and Mycobacterium tuberculosis to those of closely related species - Escherichia coli, Streptococcus pyogenes and Mycobacterium leprae, respectively - we have identified an unusual and previously unobserved feature of bacterial genome structure. Scatterplots of the conserved sequences (both DNA and protein) between each pair of species produce a distinct X-shaped pattern, which we call an X-alignment. The key feature of these alignments is that they have symmetry around the replication origin and terminus; that is, the distance of a particular conserved feature (DNA or protein) from the replication origin (or terminus) is conserved between closely related pairs of species. Statistically significant X-alignments are also found within some genomes, indicating that there is symmetry about the replication origin for paralogous features as well. CONCLUSIONS: The most likely mechanism of generation of X-alignments involves large chromosomal inversions that reverse the genomic sequence symmetrically around the origin of replication. The finding of these X-alignments between many pairs of species suggests that chromosomal inversions around the origin are a common feature of bacterial genome evolution.

Bacteria↗
PubMed2003

Complex protein-DNA dynamics at the latent origin of DNA replication of Epstein-Barr virus.

The sequential binding of the origin recognition complex (ORC), Cdc6p and the minichromosome maintenance proteins (MCM2-7) mediates replication competence at eukaryotic origins of DNA replication. The latent origin of Epstein-Barr virus, oriP, is a viral origin known to recruit ORC. OriP also binds EBNA1, a virally encoded protein that lacks any activity predicted to be required for replication initiation. Here, we used chromatin immunoprecipitation and chromatin binding to compare the cell-cycle-dependent binding of pre-RC components and EBNA1 to oriP and to global cellular chromatin. Prereplicative-complex components such as the Mcm2p-Mcm7p proteins and HsOrc1p are regulated in a cell-cycle-dependent fashion, whereas other HsOrc subunits and EBNA1 remain constantly bound. In addition, HsOrc1p becomes sensitive to the 26S proteasome after release from DNA during S phase. These results show that the complex protein-DNA dynamics at the viral oriP are synchronized with the cell division cycle. Chromatin-binding and chromatin-immunoprecipitation experiments on G0 arrested cells indicated that the ORC core complex (ORC2-5) and EBNA1 remain bound to chromatin and oriP. HsOrc6p and the MCM2-7 complex are released in resting cells. HsOrc1p is partly liberated from chromatin. Our data suggest that origins remain marked in resting cells by the ORC core complex to ensure a rapid and regulated reentry into the cell cycle. These findings indicate that HsOrc is a dynamic complex and that its DNA binding activity is regulated differently in the various stages of the cell cycle.

Animals↗
PubMed1999

Replication origins of mammalian chromosomes: the happy few.

Replication of eukaryotic cell genomes is a tightly controlled process occurring once and only once per cell cycle. Replication initiates at several thousand origins, whose cis-acting sequences and trans-acting proteins have been partially characterized in the yeast S. cerevisiae in the last few years. In contrast, identification of origins of DNA replication in mammalian cells have proven much more difficult. Currently, less then 20 bona fide mammalian origins have been identified, of which only few characterized in detail. Here we discuss the available methods for origin identification in mammalian DNA and the main results, sometimes controversial, so far generated by their application. In particular, we review the currently available information concerning the three best characterized origins, namely those in the lamin B2 and b-globin gene domains in human cells and the one located downstream of the dihydrofolate reductase gene in hamster cells.

Animals↗
PubMed2006

Replication initiation from a novel origin identified in the Th2 cytokine cluster locus requires a distant conserved noncoding sequence.

Lineage commitment of Th cells is associated with the establishment of specific transcriptional programs of cytokines. However, how Th cell differentiation affects the program of DNA replication has not been addressed. To gain insight into interplays between differentiation-induced transcription regulation and initiation of DNA replication, we took advantage of an in vitro differentiation system of naive T cells, in which one can manipulate their differentiation into Th1 or Th2 cells. We searched for replication origins in the murine IL-4/IL-13 locus and compared their profiles in the two Th cell lineages which were derived in vitro from the same precursor T cells. We identified a replication origin (ori(IL-13)) downstream from exon 4 of IL-13 and showed that this origin functions in both Th2 and Th1 cells. A distant regulatory element called CNS-1 (conserved noncoding sequence 1) in the IL-4/IL-13 intergenic region coincides with a Th2-specific DNase I-hypersensitive site and is required for efficient, coordinated expression of Th2 cytokines. Replication initiation from ori(IL-13) is significantly reduced in Th1 and Th2 cells derived from CNS-1-deficient mice. However, the replication timing of this locus is consistently early during S phase in both Th1 and Th2 cells under either the wild-type or CNS-1 deletion background. Thus, the conserved noncoding element in the intergenic region regulates replication initiation from a distant replication origin in a manner independent from its effect on lineage-specific transcription but not the replication timing of the segment surrounding this origin.

Animals↗
PubMed1990

Impacts and the origin of life.

As living creatures, all of us have some interest in the question of how life originated. To some, the question is more religious than scientific; nonetheless, a small but dedicated group of scientists spend their careers trying to answer it from a rational standpoint. Logically, the question can be broken down into the three standard divisions of any mystery: When did life originate? Where did it originate? And how did it originate? Of these three sub-questions the last is by far the most difficult and I will make no attempt to address it here. I will however take a personal look at the two easier parts of the problem. In particular, I will outline my current view of the physical environment of the early Earth, and I will try to show how observations of other solar system bodies, especially our own Moon, provide clues as to when and where life could have originated.

Atmosphere↗
PubMed2005

Controversies on the origin of life.

Different viewpoints, many with deep philosophical and historical roots, have shaped the scientific study of the origin of life. Some of these argue that primeval life was based on simple anaerobic microorganisms able to use a wide inventory of abiotic organic materials (i.e. a heterotrophic origin), whereas others invoke a more sophisticated organization, one that thrived on simple inorganic molecules (i.e. an autotrophic origin). While many scientists assume that life started as a self-replicative molecule, the first gene, a primitive self-catalytic metabolic network has also been proposed as a starting point. Even the emergence of the cell itself is a contentious issue: did boundaries and compartments appear early or late during life's origin? Starting with a recent definition of life, based on concepts of autonomy and open-ended evolution, it is proposed here that, firstly, organic molecules self-organized in a primordial metabolism located inside protocells. The flow of matter and energy across those early molecular systems allowed the generation of more ordered states, forming the cradle of the first genetic records. Thus, the origin of life was a process initiated within ecologically interconnected autonomous compartments that evolved into cells with hereditary and true Darwinian evolutionary capabilities. In other words, the individual existence of life preceded its historical-collective dimension.

Biological Evolution↗
PubMed1992

Fever of unknown origin in the 1980s. An update of the diagnostic spectrum.

OBJECTIVE: To determine the relative proportions of the diagnostic categories in patients with fever of unknown origin who were examined in the 1980s. STUDY DESIGN: Prospective case series. SETTING: General Internal Medicine Service based at University Hospital, Leuven, Belgium. PATIENTS: One hundred ninety-nine consecutive patients meeting the classic criteria of fever of unknown origin who were treated in the 1980s. MAIN OUTCOME MEASUREMENT: The final diagnosis established at discharge or during follow-up. RESULTS: Infections were found in 45 patients (22.6%), tumors were found in 14 (7%), multisystem diseases were found in 42 (21.5%), drug-related fever was found in six (3%), factitious fever was found in seven (3.5%), habitual hyperthermia was found in five (2.5%), miscellaneous diseases were found in 29 (14.5%), and no diagnosis was reached in 51 (25.6%). CONCLUSIONS: Tumors were a less important cause of fever of unknown origin in the 1980s. The same holds true for some infectious diseases, such as abscesses and hepatobiliary disorders. Multisystem diseases were more frequently found, and the number of undiagnosed cases increased. Although these shifts in the disease spectrum in fever of unknown origin most probably resulted from a constellation of factors, we suspect that these changes are mainly due to easy and early diagnosis by new diagnostic modalities, such as ultrasonography and computed tomography, of previously common causes of fever of unknown origin.

Abscess↗
PubMed1994

Association of origin binding protein and single strand DNA-binding protein, ICP8, during herpes simplex virus type 1 DNA replication in vivo.

The herpes simplex virus type 1 (HSV-1) origin binding protein (UL9 protein) interacts specifically with the HSV-1 encoded single strand DNA-binding protein ICP8 (Boehmer, P.E. and Lehman, I.R. (1994) Proc. Natl. Acad. Sci. U.S.A. 90, 8444-8448). A UL9 mutant protein (UL9DM27) that lacks the C-terminal 27 amino acids shows normal origin-specific DNA binding and retains its DNA-dependent ATPase and helicase activities, but has a greatly reduced affinity for ICP8. The extreme C-terminal portion of the UL9 protein is therefore required for ICP8 binding. The helicase activity of the UL9DM27 protein is approximately 8-fold greater than that of the wild type UL9 protein and is not stimulated by ICP8. The UL9DM27 protein has a reduced ability to replicate origin-containing plasmids in vivo. Consequently, the interaction between the UL9 protein and ICP8 is likely to be important for origin-dependent DNA replication in vivo, presumably to promote efficient unwinding of the DNA at an HSV-1 origin of DNA replication.

Amino Acid Sequence↗
PubMed1996

ORC- and Cdc6-dependent complexes at active and inactive chromosomal replication origins in Saccharomyces cerevisiae.

We have developed a genomic footprinting protocol which allows us to examine protein-DNA interactions at single copy chromosomal origins of DNA replication in the budding yeast Saccharomyces cerevisiae. We show that active replication origins oscillate between two chromatin states during the cell cycle: an origin recognition complex (ORC)-dependent post-replicative state and a Cdc6p-dependent pre-replicative state. Furthermore, we show that both post- and pre-replicative complexes can form efficiently on closely apposed replicators. Surprisingly, ARS301 which is active as an origin on plasmids but not in its normal chromosomal location, forms ORC- and Cdc6p-dependent complexes in both its active and inactive contexts. Thus, although ORC and Cdc6p are essential for initiation, their binding is not sufficient to dictate origin use.

Base Sequence↗
PubMed1998

Cortical metastatic lesions of the appendicular skeleton from tumors of known primary origin.

BACKGROUND AND OBJECTIVES: Metastatic disease represents the most common neoplastic process involving bone. Recently, a small subset of cortical based metastatic lesions has been identified. We attempted to delineate the incidence, origin, location, and possible significance of these lesions within an orthopaedic patient population. METHODS: A chart and radiographic review of patients treated for metastatic disease to bone over a 17-year period was performed. Inclusion criteria for lesions were as follows: 1) an appendicular skeletal site, 2) histopathologic confirmation of origin, and 3) presence within a patient diagnosed with a single, known neoplastic process. The lesions were classified as either cortical or medullary based. RESULTS: Eighty-three lesions (70 patients) satisfied inclusion criteria. Most lesions were of pulmonary (26), breast (22), renal (16), or prostatic (8) tumor origin. Eighteen lesions (22%) from 15 patients were identified as cortical and represented initial presentation in 7 patients. These lesions were of pulmonary (11), renal (5), and breast (2) tumor origin. CONCLUSIONS: Cortical based metastases within the appendicular skeleton may occur more frequently than previously expected. While tumors of pulmonary and renal origin accounted for 42 of the 83 (51%) appendicular lesions, they were responsible for 16 of the 18 (89%) cortical metastases. This preponderance of pulmonary and renal metastases to the cortex is consistent with previously published reports. Our findings may be of value when diagnosing and treating patients whose initial presentation is a cortically based lesion.

Adenocarcinoma↗
PubMed1998

Dual morphology and topography of the corticothalamic terminals originating from the primary, supplementary motor, and dorsal premotor cortical areas in macaque monkeys.

In the motor, somatosensory, and auditory systems of rodents and cats, the corticothalamic connection is composed of a main projection formed by small endings and a minor projection terminating with giant endings. To establish whether the corticothalamic projection originating from motor cortical areas in primates exhibits the same duality, the anterograde tracer biotinylated dextran amine was injected in eight macaque monkeys in the primary motor (M1; n = 3), the supplementary motor (SMA; n = 3) and the dorsal premotor (PMd; n = 2) cortical areas to label corticothalamic axons. The corticothalamic projection originating from these three motor cortical areas was characterized by the presence of axon terminals constituting the same two types of endings, observed both as boutons en passant and terminaux. The population of small endings exhibited a mean cross-sectional maximum diameter of 0.95 microm (S.D. = 0.23), a range of diameters not overlapping that of giant endings (mean diameter = 3.46 microm, S.D. = 0.74 microm). Topographically, the giant endings originating from M1 were located in the same thalamic nucleus (ventroposterolateral nucleus, oral part) in which the small endings were found. In contrast, the giant endings originating from SMA and PMd were located in a thalamic nucleus (mediodorsal nucleus) distinct from the main termination zone formed by small endings. Along the rostrocaudal axis, the giant endings were distributed in a restricted zone, irrespective of the origin of the projection (M1, SMA, PMd). The dual morphology of corticothalamic endings, previously found in rodents and cats, is present in the motor system of subhuman primates for both primary and nonprimary motor cortical areas.

Animals↗
PubMed1996

Relative frequency of a subclavian vs. a transverse cervical origin for the dorsal scapular artery in humans.

BACKGROUND: The origin of the dorsal scapular artery to the rhomboid muscles in humans has been the subject of uncertainty. The present study sought to clarify which of its two most common sources (the transverse cervical artery or the subclavian artery) is the major source of the dorsal scapular artery. METHODS: Gross anatomical dissection was used to visualize the origin and course of the dorsal scapular artery in human cadavers. RESULTS: We found that the dorsal scapular artery typically arises from either of two main sources: the subclavian artery (about 75% of all sides) or the transverse cervical artery (about 25% of all sides). Subclavian origins were approximately equally divided between its second and third part. Other origins for the dorsal scapular artery were negligible in frequency. Those dorsal scapular arteries that arose from the subclavian artery passed between the upper and middle or middle and lower trunks of the brachial plexus to course to the rhomboid muscles. In the case of transverse cervical artery origin, the dorsal scapular artery arose as a branch that passed deep to the levator scapulae muscle before coursing to the rhomboid muscles. No noteworthy differences were observed between males and females. CONCLUSIONS: These results strongly support the simple view, which does not appear widely accepted, that the subclavian artery is the most common source of the dorsal scapular artery to the rhomboid muscles and the transverse cervical artery a major but secondary source.

Aged↗
PubMed1996

Embryonic origin and fate of chondroid tissue and secondary cartilages in the avian skull.

BACKGROUND: Chondroid tissue is an intermediate calcified tissue, mainly involved in desmocranial morphogenesis. Often associated with secondary cartilages, it remained of unprecise embryonic origin. METHODS: The latter was studied by performing isotopic isochronic grafts of quail encephalon onto 30 chick embryos. The so-obtained chimeras were sacrificed at the 9th, 12th, and 14th day of incubation. The contribution of graft- and host-derived cells to the histogenesis of chondroid tissue, bone, and secondary cartilages was analyzed on both microradiographs of thick undecalcified sections and on classical histological sections after several DNA or ECM specific staining procedures. RESULTS: Chondroid tissue is deposited in the primitive anlage of all membranous bones of the avian skull. Also present on their sutural edges, it uniformly arises from the neural crest. In the face, bone and secondary cartilages share this mesectodermal origin. However, secondary cartilages located along the basal chondrocranium and bone formed on the chondroid primordium of the cranial vault, originate from the cephalic mesoderm. CONCLUSIONS: These facts provide evidence that chondroid tissue arises from a specific differentiation of neural crest derived cells and that this original skeletogenic program differs from that of secondary chondrogenesis. Moreover, they obviously indicate that in membraneous bone ontogenesis, chondroid tissue replaces functions devoted to mesodermal primary cartilages of the cranial base, and so corroborates at the tissue level, the dual embryonic and phyletic origin of the skull.

Age Factors↗
PubMed1997

Entorhinal cortex of the rat: cytoarchitectonic subdivisions and the origin and distribution of cortical efferents.

The origins and terminations of entorhinal cortical projections in the rat were analyzed in detail with retrograde and anterograde tracing techniques. Retrograde fluorescent tracers were injected in different portions of olfactory, medial frontal (infralimbic and prelimbic areas), lateral frontal (motor area), temporal (auditory), parietal (somatosensory), occipital (visual), cingulate, retrosplenial, insular, and perirhinal cortices. Anterograde tracer injections were placed in various parts of the rat entorhinal cortex to demonstrate the laminar and topographical distribution of the cortical projections of the entorhinal cortex. The retrograde experiments showed that each cortical area explored receives projections from a specific set of entorhinal neurons, limited in number and distribution. By far the most extensive entorhinal projection was directed to the perirhinal cortex. This projection, which arises from all layers, originates throughout the entorhinal cortex, although its major origin is from the more lateral and caudal parts of the entorhinal cortex. Projections to the medial frontal cortex and olfactory structures originate largely in layers II and III of much of the intermediate and medial portions of the entorhinal cortex, although a modest component arises from neurons in layer V of the more caudal parts of the entorhinal cortex. Neurons in layer V of an extremely laterally located strip of entorhinal cortex, positioned along the rhinal fissure, give rise to the projections to lateral frontal (motor), parietal (somatosensory), temporal (auditory), occipital (visual), anterior insular, and cingulate cortices. Neurons in layer V of the most caudal part of the entorhinal cortex originate projections to the retrosplenial cortex. The anterograde experiments confirmed these findings and showed that in general, the terminal fields of the entorhinal-cortical projections were densest in layers I, II, and III, although particularly in the more densely innervated areas, labeling in layer V was also present. Comparably distributed, but much weaker projections reach the contralateral hemisphere. Our results show that in the rat, hippocampal output can reach widespread portions of the neocortex through a relay in a very restricted part of the entorhinal cortex. However, most of the hippocampal-cortical connections will be mediated by way of entorhinal-perirhinal-cortical connections. We conclude that, in contrast to previous notions, the overall organization of the hippocampal-cortical connectivity in the rat is largely comparable to that in the monkey.

Amygdala↗
PubMed1998

Abnormal origin of internal thoracic and vertebral arteries.

The aim of this study was to evaluate the variability of the origin of the internal thoracic and vertebral arteries after a cadaver demonstrated abnormal origins for both vessels. The arteries were studied in 60 adult cadavers and measurements taken to adjacent structures. In one cadaver the right internal thoracic artery originated from the third part of the subclavian artery (one of 120 arteries; 0.83%). The same cadaver presented with the left vertebral artery originating directly from the aortic arch between the left common carotid and left subclavian arteries. Two other cadavers also presented with abnormal vertebral arteries, making it three of 60 left vertebral arteries (5%). These results are comparable to the established range in the literature. The internal thoracic artery is used for revascularization in coronary artery diseases and as this area is also used for subclavian vein catheterization, it is important to be aware of this rare variation concerning the internal thoracic artery. This study reports an important variation in the origins of the internal thoracic and vertebral artery in a singular cadaver.

Adult↗