Showing papers on "Gene published in 1972"
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TL;DR: A sustained effort is proposed to be made to formulate a complete set of ethicoscientific criteria to guide the development and clinical application of gene therapy techniques, which could go a long way toward ensuring that gene therapy is used in humans only in those instances where it will prove beneficial, and toward preventing its misuse through premature application.
Abstract: In our view, gene therapy may ameliorate some human genetic diseases in the future. For this reason, we believe that research directed at the development of techniques for gene therapy should continue. For the foreseeable future, however, we oppose any further attempts at gene therapy in human patients because (i) our understanding of such basic processes as gene regulation and genetic recombination in human cells is inadequate; (ii) our understanding of the details of the relation between the molecular defect and the disease state is rudimentary for essentially all genetic diseases; and (iii) we have no information on the short-range and long-term side effects of gene therapy. We therefore propose that a sustained effort be made to formulate a complete set of ethicoscientific criteria to guide the development and clinical application of gene therapy techniques. Such an endeavor could go a long way toward ensuring that gene therapy is used in humans only in those instances where it will prove beneficial, and toward preventing its misuse through premature application. Two recent papers have provided new demonstrations of directed genetic modification of mammalian cells. Munyon et al. (44) restored the ability to synthesize the enzyme thymidine kinase to thymidine kinase-deficient mouse cells by infection with ultraviolet-irradiated herpes simplex virus. In their experiments the DNA from herpes simplex virus, which contains a gene coding for thymidine kinase, may have formed a hereditable association with the mouse cells. Merril et al. (45) reported that treatment of fibroblasts from patients with galactosemia with exogenous DNA caused increased activity of a missing enzyme, alpha-D-galactose-l-phosphate uridyltransferase. They also provided some evidence that the change persisted after subculturing the treated cells. If this latter report can be confirmed, the feasibility of directed genetic modification of human cells would be clearly demonstrated, considerably enhancing the technical prospects for gene therapy.
671 citations
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TL;DR: The review considers information from mammalian embryology relevant to X‐chromosome inactivation, and from X‐inactivation relevant to mammalian embryologists, to derive conclusions about inactivation and its role in embryology.
Abstract: Summary
1. The review considers information from mammalian embryology relevant to X-chromosome inactivation, and from X-inactivation relevant to mammalian embryology.
2. Properties of the inactive-X, by which it may be recognized are: sex chromatin, heteropycnosis, late replication and the absence of gene product. Each of these has advantages and disadvantages in particular circumstances. In some species the X carries constitutive heterochromatin, which must be distinguished from the facultative region.
3. The time of X-chromosome inactivation can be estimated from the time of appearance of sex chromatin or late replication, or inferred from the appearance of heterozygotes for X-linked genes or of experimental chimaeras. The estimated time varies with species, and in the mouse and rabbit is near the time of increase in RNA synthesis.
4. Whereas in eutherian mammals either the maternally or the paternally derived X may be inactivated in different cell lines, in marsupials the paternal X is always the inactive one.
5. During development various factors act to distort the patterns produced by random X-inactivation. These factors include cell selection, transfer of gene product, and migration and mingling of cells.
6. There is no clear evidence that X-chromosome inactivation is not complete.
7. In female germ cells both X-chromosomes appear to be active. In male ones both X and Y appear inactive during most of spermatogenesis, although probably in early stages all X chromosomes present are active.
8. The active and inactive X-chromosomes may be differentiated by presence or absence of some non-histone protein or other polyanionic substance.
9. If the genes concerned in synthesis or attachment of this substance are on the X-chromosome then the differentiation will be self-maintaining.
10. The initiation of the differentiation requires either the attachment of different X-chromosomes to different sites, or some interaction of X-linked and autosomal genes, concerned in inducing or repressing activity. Some possible models are discussed.
586 citations
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TL;DR: Temperature-shift experiments and analysis of SV40 viralDNA replication by gel electrophoresis have provided strong evidence that the ts gene product of the three mutants is directly required to initiate each new round of viral DNA replication but is not required to complete a cycle which has already begun.
Abstract: Three temperature-sensitive (ts) mutants of simian virus 40 (SV40) in complementation group A (tsA7, tsA28, tsA30) have been isolated and characterized in permissive and restrictive host cells. At 41 C in the AH line of African green monkey kidney cells, the mutants are deficient in an early function required to produce infectious viral deoxyribonucleic acid (DNA). Temperature-shift experiments and analysis of SV40 viral DNA replication by gel electrophoresis have provided strong evidence that the ts gene product of the three mutants is directly required to initiate each new round of viral DNA replication but is not required to complete a cycle which has already begun. The synthesis of mutant DNA molecules themselves can be initiated by a nonmutant gene product in viral complementation studies at 41 C. The cell, however, cannot substitute a host function to provide the initiator required for the replication of free viral DNA. The viral initiator is also required to establish the stable transformation of 3T3 cells.
520 citations
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499 citations
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TL;DR: By characterization of fragments, isolated from a nuclease digest of MS2 RNA, the entire nucleotide sequence of the coat gene was established and a “flower”-like model is proposed for the secondary structure.
Abstract: By characterization of fragments, isolated from a nuclease digest of MS2 RNA, the entire nucleotide sequence of the coat gene was established. A “flower”-like model is proposed for the secondary structure. The genetic code makes use of 49 different codons to specify the sequence of the 129 amino-acids long coat polypeptide.
476 citations
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TL;DR: It is concluded that a “correction” mechanism must operate to spread a mutation in one spacer sequence to the neighboring spacers faster than new changes arise in these genes.
410 citations
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TL;DR: This book is very referred for you because it gives not only the experience but also lesson, that's not about who are reading this dna protein interactions book but about this book that will give wellness for all people from many societies.
Abstract: Where you can find the dna protein interactions easily? Is it in the book store? On-line book store? are you sure? Keep in mind that you will find the book in this site. This book is very referred for you because it gives not only the experience but also lesson. The lessons are very valuable to serve for you, that's not about who are reading this dna protein interactions book. It is about this book that will give wellness for all people from many societies.
379 citations
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TL;DR: In this paper, electron microscopy reveals that the structure of the gene 5 protein complex with single-stranded DNA is quite different: whereas gene 32 protein forces the DNA into an extended linear conformation, the gene5 protein coalesces two protein-covered DNA stands into a helical, rodlike structure.
271 citations
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TL;DR: The genes for the protein silk fibroin were quantitated by hybridizaton of purified fibro in messenger RNA with the DNA from several tissues of the silk-worm Bombyx mori to rule out specific gene amplification as an explanation for the specialized synthesis of Fibroin by posterior silk gland cells.
260 citations
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TL;DR: It is hard to imagine that eukaryotes, being presented with such a superb mechanism for controlling DNA transcription, would totally discard it and opt for something different, but several observations suggest that higher organisms may have picked up a number of fundamental genetic tricks from their lowly predecessors.
Abstract: Biochemical and genetic studies have produced a vast fund of knowledge concerning gene action and regulation in prokaryotes In these organisms the DNA is exposed rather nakedly to the world, protected primarily by the cell membrane In eukaryotes the DNA seems far better shielded, being enmeshed in histone and nonhistone proteins and sequestered behind both the cell and the nuclear membrane These differences have led to a considerable degree of caution in the application of this knowledge of prokaryotes to problems of gene regulation in eukaryotes, and rightly so There are, however, several observations which suggest that higher organisms may have picked up a number of fundamental genetic tricks from their lowly predecessors It has frequently been suggested that eukaryotes must do things differently from prokaryotes, until proven otherwise It may be prudent to reverse this line of thought and suggest that they do things the came until proven different The following similarities suggest this (1) T he basic genetic dogmas concerning DNA replication, transcription, andlation are similar, (2) The genetic code is the same (3) Both systems appear to make use of cyclic AMP as a basic mediator for, humoral or diffusible, signals (4) In both systems DNA synthesis may be controlled at membranes (5) Both make use of different types of RNA polymerase and RNA polymerase cofactors (6) Recent studies of polylysine binding to chromatin suggest the eukaryotic DNA may not be so thoroughly enmeshed in Protein as once thought (7) The visualization of genes in action by electron microscopic techniques intimates that genes are spaced and read in a similar manner And finally, (8) merely because the clustering of related genes is unusual in higher organisms is no reason in itself to totally discard the promoter-operator-repressor concept as a way of regulating single structural genes This system has provided an immense amount of data concerning the manner in which proteins interact with specific DNA sequences to control the attachment and utilization of RNA polymerase It is hard to imagine that eukaryotes, being presented with such a superb mechanism for controlling DNA transcription, would totally discard it and opt for something different It is far more likely that they would build on to this solid foundation
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TL;DR: SCIENCE is published weekly, except the last week in December, but with an extra issue on the third Tuesday in November, by the American Association for the Advancement Science, 1515 Massachusetts Ave., NW, Washington, D.C. 20005.
Abstract: SCIENCE is published weekly, except the last week in December, but with an extra issue on the third Tuesday in November, by the American Association for the Advancement Science, 1515 Massachusetts Ave., NW, Washington, D.C. 20005. Now combined with The Scientific Monthly. Second-class postage paid at Washington, D.C. Copyright t 1972 the American Association for the Advancement of Science. Annual subscription $20; foreign postage: Americas $3; overseas $5; 'air freight to Europe, North Africa, Near East $ single copies $1 (back issues, $2) except Guide to Scientific Instruments which is $4. School year subscription: 9 months, $15; 10 mnh,$67,Poide 4 weeks notice change of address, giving new and old address and zip codes. Send a recent address label. SCIENCE is indexed in the Reader's Guide to Periodical LIteature. EDITORIAL
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TL;DR: The denaturation map derived with bacteriophage lambda DNA closely resembles that obtained earlier with heat and alkaline denaturation in the absence of protein, indicating that the protein preferentially invades A + T rich double-helical regions, without a requirement for a physical discontinuity such as a cleaved phosphodiester bond or a double-stranded end.
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TL;DR: The amino acid sequence of urinary β2-microglobulin has been partially determined and found to be related to the constant region of IgG immunoglobulin heavy chain.
Abstract: The amino acid sequence of urinary beta(2)-microglobulin has been partially determined and found to be related to the constant region of IgG immunoglobulin heavy chain. beta(2)-Microglobulin is present in normal individuals. Its gene may have evolved from an immunoglobulin gene by the use of an unusually located start signal for initiating synthesis of the polypeptide.
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TL;DR: It was found that many insertions which often arise as strongly polar mutations consist of only a few “foreign” DNA sequences.
Abstract: It was found that many insertions which often arise as strongly polar mutations consist of only a few “foreign” DNA sequences. The most commonly observed “short” polar IS1 insertions are all comprised of the same DNA with a duplex length of 750±80 nucleotide pairs. This insertable IS1 DNA can be integrated with either orientation into the genome at various positions in the lac and gal operons of E. coli; however, the inserted sequence is not permuted. The r14 polar insertion in gene cII of phage λ also consists of the same IS1 DNA (Hirsch et al., 1972 b). “Long” insertions (1170 to 1490 nucleotide pairs) were detected in the lac (IS3) and gal (IS2, IS4) operons and in the y and P-Q regions (IS2) of the λ genome and measured as single-strand loops in the l/r heteroduplex DNA. The insertions in the latter two positions are homologous, although those found in the P-Q region do not exhibit any obvious polarity.
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TL;DR: This chapter discusses the origin of the wide species variation in nuclear DNA content, which is attributable to the amplification or reduction of DNA segments within chromosomes.
Abstract: Publisher Summary This chapter discusses the origin of the wide species variation in nuclear DNA content. Evolution depends upon the selection of phenotypes displaying adaptive changes of a heritable nature. The generation of such phenotypes depends on the alteration of genetic information embodied within the DNA of the chromosomes. As for evolutionary change in DNA amount , there is a progression from low DNA content in primitive phyla, such as bacteria to high DNA content in cells of sophisticated higher plants and animals. The causes of change in DNA amount are illustrated in the chapter. Polyploidy, common in plant groups such as the angiosperms and pteridophytes, is a special case as it involves amplification of all genes and all base sequences of the haploid complement. There is an extensive and widespread variation in DNA amount, which is independent of alteration in chromosome number. This is attributable to the amplification or reduction of DNA segments within chromosomes.
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TL;DR: A kinetic analysis of the amounts of gene products indicated that the synthesis of individual late proteins in phage λ seems to be initiated in an orderly fashion, related to the distance of the genes from the late main promoter between genes Q and S, and indicates the presence of a remarkable control mechanism for gene expression of the left arm.
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TL;DR: Gene 5 protein of bacteriophage fd was purified from phage infected bacteria and increases the template activity of a viral replicative form DNA for polymerase II at low concentrations.
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TL;DR: This simple theory provides a function for non-histone proteins and an explanation for the large size of eukaryotic genomes, repetitive sequences in DNA, HnRNA and “processing” of nuclear RNA.
Abstract: This simple theory provides a function for non-histone proteins and an explanation for the large size of eukaryotic genomes, repetitive sequences in DNA, HnRNA and “processing” of nuclear RNA.
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TL;DR: It is inferred that Mu-1 can integrate at a very large number of chromosomal sites, which makes it distinct from other known temperate coliphages; the lambdoid phages attach at a particular site, P2 phage attaches at a limited number of sites and P1 resides in the cell as a plasmid6.
Abstract: THE temperate bacteriophage Mu-1 can induce mutations at many different loci in the genome of its host bacterium Escherichia coli K12 (see ref. 1). The mutations are assumed to arise by the insertion of Mu-1 DNA within the affected genes, as the sites of mutations are inseparable from the prophage sites by genetic criteria2, 3. It has been inferred therefore that Mu-1 can integrate at a very large number of chromosomal sites. This attribute of Mu-1 makes it distinct from other known temperate coliphages; the lambdoid phages attach at a particular site4, P2 phage attaches at a limited number of sites5 and P1 resides in the cell as a plasmid6.
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TL;DR: The stability of the mRNA can account for the marked progressive increase in translation, within phase II, without the necessity of postulating a parallel increase in the transcriptional activity.
Abstract: Publisher Summary This chapter discusses the zymogen cell differentiation for specific protein synthesis. Development of terminally differentiated cells specialized for specific protein synthesis involves the sequential and coordinated occurrence of several steps. Some of these are: differential mitosis, morphogenesis, mitosis or polyploidization, elaboration of an appropriate cytoplasm, synthesis of the specific cell product at a low and then high rate, and finally turning off or the modulation of specific synthesis. Continuous increase in specific protein synthesis during phase I and II is quite significant. If the specific gene is very active in transcription, differential stability would lead to mRNA accumulation. Thus, the stability of the mRNA can account for the marked progressive increase in translation, within phase II, without the necessity of postulating a parallel increase in the transcriptional activity. The absolute increase in specific protein synthesis during phase I is much slower, suggesting that accumulation and perhaps specific gene transcription is occurring more slowly at that time. Assuming that protein synthesis is proportional to mRNA content, the increase in protein synthesis during phase II measures the rate, at which specific mRNA accumulates in the system. This rate of accumulation is compatible with the existence of a single copy of the differentiation-specific gene per genome.
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TL;DR: Four new small polypeptides are associated with DNA-dependent RNA polymerase from E. coli after infection with T4 phage, and their molecular weights range from 10,000 to 22,000, as detected by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate.
Abstract: Four new small polypeptides are associated with DNA-dependent RNA polymerase from E. coli after infection with T4 phage. The new polypeptides are easily detected in RNA polymerase from E. coli cells labeled with amino acids after phage infection. Their molecular weights range from 10,000 to 22,000, as detected by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. All four polypeptides are found after infection with either wild-type T4 phage or T4 early amber mutants in genes 44, 42, 47, and 46. None of the polypeptides is labeled significantly before 5 min after infection at 30°. When two maturation-defective amber mutants in gene 55 of T4 phage are used for infection, a polypeptide with a molecular weight of 22,000 is absent. When a maturation-defective amber mutant in gene 33 of T4 phage is used, another small protein is absent.
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TL;DR: The chromosomal location of one of the two murine leukemia virus-inducing loci of AKR mice has been determined, and this identification of a closely linked gene whose phenotype is independent of virus expression should facilitate analysis of the biologic importance of the Akv-1 locus.
Abstract: The chromosomal location of one of the two murine leukemia virus-inducing loci of AKR mice has been determined. The locus, which appears to be the integrated genome of the virus, is designated Akv-1, and is on linkage group 1, 12 map units from Gpi-1, with gene order c-Gpi-1-Akv-1. This identification of a closely linked gene whose phenotype is independent of virus expression should facilitate analysis of the biologic importance of the Akv-1 locus.
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TL;DR: Measurement of MTV-specific nucleotide sequences in DNA from high and low tumour incidence mouse strains found that DNA from both GR and C57BL/6 strains accelerates the reannealing of the labelled polymerase product, causing an apparent reduction in the C0t½ values consistent with the presence of sixty to a hundred copies of those sequences in both strains.
Abstract: IN most mouse strains with a high incidence of mammary tumours, mouse mammary tumour virus (MTV) is transmitted only in the milk1,2, but in GR mice it is also transmitted by the gametes of both sexes in a simple autosomal dominant pattern2,3. Since inheritance of an MTV susceptibility gene cannot be shown to explain these observations2, either there are MTV genes in GR but not in low incidence strains or the mice inherit factors governing the expression of such genes3. In the latter case, both types would contain virus-specific genes, but only the GR mice would consistently express them. To choose between these alternatives, we have measured MTV-specific nucleotide sequences in DNA from high and low tumour incidence mouse strains4. Unlabelled cellular DNA was tested for virus-specific sequences by its capacity to accelerate the reassociation of labelled double stranded DNA transcribed in vitro by the MTV virion reverse transcriptase. DNA from both GR (MTV +) and C57BL/6 (MTV−) strains accelerates the reannealing of the labelled polymerase product, causing an apparent reduction in the C0t½ values consistent with the presence of sixty to a hundred copies of those sequences in both strains.
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TL;DR: Structural aspects of the activity of specific genes are demonstrated here using representatives of both eukaryotic and prokaryotic cell types using the use of relatively simple techniques for isolating portions of active genomes.
Abstract: Publisher Summary The numerous electron microscope autoradiographic studies of eukaryotic cells show that RNA synthesis is localized in dispersed chromatin in both nucleolar and non-nucleolar compartments of the nucleus. Alternatively, autoradiography of thin sections of pulse-labeled bacteria shows the localization of RNA synthesis near the interface of the ribosome-containing areas of the cell and the nucleoid regions that contain most of the bacterial DNA. An example of the structural resolution of genetic activity obtainable by thin-sectioning methods is presented in this chapter. In none of the thin-section studies with either eukaryotic or prokaryotic cells, however, could a distinct genetic unit be resolved within the regions active in RNA synthesis. More recently, direct visualization of the fine structure of individual, active genes in both cell types has been accomplished through novel isolation techniques. This chapter discusses the current status of these studies. Structural aspects of the activity of specific genes are demonstrated here using representatives of both eukaryotic and prokaryotic cell types. In both cases, inherent characteristics of the cells permitted the use of relatively simple techniques for isolating portions of active genomes.
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TL;DR: The number of copies of the ribosomal RNA genes varies considerably between the different plant species studied, it does seem, however, that there is no gross amplification or deletion of these genes during the development of a particular plant.
Abstract: The number of copies of the ribosomal RNA genes varies considerably between the different plant species studied. It does seem, however, that there is no gross amplification or deletion of these genes during the development of a particular plant.
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TL;DR: It is shown that in experiments performed in conditions of DNA excess, Bishop et al. obtained a much lower estimate, of about five globin genes per genome, when duck 9S RNA was hybridized to excess duck DNA.
Abstract: IT is crucial to all our ideas about the structure of eukaryotic chromosomes that we should have estimates of the numbers of copies of typical genes in the genome. Genetic evidence argues for a single copy of each gene but this is difficult to reconcile with experimental evidence that some genes, for example those specifying histones1 and ribosomal RNA2, are reiterated some hundreds or thousands of times without significant divergencies. In a previous report from this laboratory3, it was estimated that globin mRNA hybridized with an amount of DNA corresponding to 50,000 copies of globin genes. These experiments were performed in conditions of RNA excess and the hybrids were of poor quality; hence they were probably relatively non-specific and the results are readily explained in terms of hybridization of a component of the RNA with a family of repetitive sequences4. Similar considerations also apply to the estimate of 60,000 copies of globin genes obtained by hybridization of avian blood 10S RNA5. More recently, in experiments performed in conditions of DNA excess, Bishop et al.6 obtained a much lower estimate, of about five globin genes per genome, when duck 9S RNA was hybridized to excess duck DNA. These experiments have been criticized7 because the relationship between the rate constants for RNA–DNA and DNA–DNA hybridization reactions is uncertain and could be changed by partial degradation of RNA; moreover, a considerable fraction of the RNA remained unreacted in the presence of excess DNA even at very high C0t values (the product of concentration of nucleic acid and incubation time expressed as mole nucleotide per litre × s).
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TL;DR: Comparative studies on the rates of labeling of RNA precursors late in infection support the earlier reported conclusion that the rate of RNA synthesis decreases considerably when DNA synthesis is blocked.
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TL;DR: Hybridization between duck DNA and duck haemoglobin mRNA shows that there is little or no reiteration of the ha Hemoglobin genes.
Abstract: Hybridization between duck DNA and duck haemoglobin mRNA shows that there is little or no reiteration of the haemoglobin genes
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01 Jan 1972TL;DR: Molecular genetics has given new insights into chromosomal structure and function, its mechanism of replication, the linear sequence of its repeating units which form the genetic code, and the process by which this code is transcribed into a specific protein structure.
Abstract: The concept that chromosomes are essential constituents of cells is nearly a hundred years old. Genetical studies have demonstrated that chromosomes are the carriers of the genes, which determine the hereditary characteristics of the organism. Molecular genetics has given new insights into chromosomal structure and function, its mechanism of replication, the linear sequence of its repeating units which form the genetic code, and the process by which this code is transcribed into a specific protein structure. The chromosomes and their genes are acknowledged to be the biological basis of human variation in health and disease.