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Showing papers on "Gene published in 1972"


Journal ArticleDOI
03 Mar 1972-Science
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


Journal ArticleDOI
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


01 Jan 1972

531 citations


Journal ArticleDOI
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



Journal ArticleDOI
12 May 1972-Nature
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


Journal ArticleDOI
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


Journal ArticleDOI
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


Journal ArticleDOI
15 Dec 1972-Science
TL;DR: Data indicate an immune response (Ir) gene specific for antigen E necessary but not sufficient for the development of hay fever, the first documentation of an Ir gene in man.
Abstract: Clinical ragweed pollenosis (hay fever) and IgE antibody production specific for antigen E (the major purified protein antigen from ragweed pollen extract) correlated closely with HL-A haplotypes in successive generations of seven families. HL-A associated IgE antibody responsiveness was antigen specific and extended also to IgE antibody production. These data indicate an immune response (Ir) gene specific for antigen E necessary but not sufficient for the development of hay fever. This appears to be the first documentation of an Ir gene in man.

290 citations


Journal ArticleDOI
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


Journal ArticleDOI
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.

Book ChapterDOI
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

Journal ArticleDOI
05 May 1972-Science
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

Journal ArticleDOI
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.

Journal ArticleDOI
TL;DR: The hypothesis that vegetative incompatibility serves as a cellular defence mechanism against genetic infection by stopping the spread of viruses and other suppressive cytoplasmic determinants from strain to strain in nature is supported.
Abstract: SUMMARY: The effect of vegetative (heterokaryon) incompatibility on the transfer of a suppressive cytoplasmically determined condition, vegetative death, from carrier to normal strains of Aspergillus amstelodami has been investigated. Cytoplasmic transfer was reduced to 15% by vegetative incompatibility compared with 100% transfer in compatible combinations. Successful transfer in incompatible combinations involved donors and recipients whose incompatibility was determined by a single gene, and transfer was completely prevented between strains differing for more than one incompatibility gene. These results support the hypothesis that vegetative incompatibility serves as a cellular defence mechanism against genetic infection by stopping the spread of viruses and other suppressive cytoplasmic determinants from strain to strain in nature. Vegetative incompatibility is likely to be important in determining the specificity of virus-host interactions in fungi.


Journal ArticleDOI
TL;DR: Molecular models have been used to demonstrate that a crossed strand-exchange between two homologous DNA molecules, a likely intermediate in genetic recombination, can be formed with all of the bases in the two double-helices remaining paired.


Journal ArticleDOI
14 Jan 1972-Science
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.

Journal ArticleDOI
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.

Journal ArticleDOI
TL;DR: Fifty mutants of Streptomyces coelicolor, having white instead of the wild-type grey colonies, were examined microscopically and genetically, finding close linked mutations possessed similar aerial mycelium structure, with few exceptions.
Abstract: SUMMARY: Fifty whi mutants of Streptomyces coelicolor, having white instead of the wild-type grey colonies, were examined microscopically and genetically. The aerial mycelium structure of the mutants was broadly classified into six types, ranging from the complete absence of any stage of sporulation to the presence of apparently normal spores. Eight map locations were discovered for whi genes, all in previously well-marked regions of the map. Closely linked mutations possessed similar aerial mycelium structure, with few exceptions.

Journal ArticleDOI
TL;DR: The theory that iron, taken up by the cell as ferric-enterochelin is only available for general cell metabolism after hydrolysis of the ligand by enterochelin esterase is supported.
Abstract: Three mutant strains of Escherichia coli have been isolated which are lacking ferric-enterochelin esterase activity. This enzyme catalyzes the hydrolysis of the enterochelin moiety of ferric-enterochelin to yield ultimately three molecules of N-2,3-dihydroxybenzoylserine. The mutants (designated fes−) were shown to be unaffected in enterochelin biosynthesis, capable of enterochelin-mediated iron uptake, and able to utilize ferric-dihydroxybenzoylserine complexes normally. When grown under iron-deficient conditions, however, they showed an absolute requirement for added iron or citrate, a phenotype characteristic of mutants defective in some part of the enterochelin system of iron uptake. These results support the theory that iron, taken up by the cell as ferric-enterochelin is only available for general cell metabolism after hydrolysis of the ligand by enterochelin esterase. The three fes− strains were shown to be affected in the B component of enterochelin esterase. The fesB gene which is probably the structural gene coding for component B of the esterase, was shown to be located at about minute 14 on the E. coli chromosome together with seven other genes involved in the enterochelin system of iron transport.

Book ChapterDOI
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.

Journal ArticleDOI
01 Jun 1972-Virology
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.

Journal ArticleDOI
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.

Journal ArticleDOI
25 Aug 1972-Nature
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.

Journal ArticleDOI
26 Apr 1972-Nature
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.

Book ChapterDOI
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.

Journal ArticleDOI
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.

Journal ArticleDOI
24 Nov 1972-Science
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.