Abstract:
:In animal cells, exogenous DNA recombines into random chromosomal sites much more frequently than it recombines into homologous sites. Free DNA ends are "recombinogenic" in both processes. To test the effects of specific ends on analogous extrachromosomal processes, we constructed a linear genome of simian virus 40 with terminal repeated sequences. After transfection into monkey cells, the model substrate can circularize by end joining (analogous to random integration) or by homologous recombination between its terminal repeats (analogous to targeted recombination). Since the two types of recombination are in competition with one another, the ratio of homologous-recombination to end-join products is a sensitive indicator of the differential effects of specific ends. Substrates with blunt ends, complementary sticky ends, or mismatched ends generated the same ratio of homologous-recombination to end-join products. However, addition of dideoxynucleotides to the 3' hydroxyls of the substrate decreased the frequency of end joining by a factor of 5-6 relative to homologous recombination. Thus, the frequency of end joining can be decreased relative to that of homologous recombination by modification of the ends of the input DNA. These results suggest an approach to altering the ratio of random to targeted integration in mammalian cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Chang XB,Wilson JHdoi
10.1073/pnas.84.14.4959subject
Has Abstractpub_date
1987-07-01 00:00:00pages
4959-63issue
14eissn
0027-8424issn
1091-6490journal_volume
84pub_type
杂志文章abstract::The rRNA intervening sequence of Tetrahymena is a catalytic RNA molecule, or "ribozyme." A tertiary-structure model of the active site of this ribozyme has been constructed based on comparative sequence analysis of related group I intervening sequences, data on the accessibility of each nucleotide to chemical and enzy...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.24.8788
更新日期:1987-12-01 00:00:00
abstract::Embryonic stem cells (derived from 129/Ola mice) containing a mutant hypoxanthine phosphoribosyltransferase gene that had been corrected in vitro in a planned manner by homologous recombination were injected into blastocysts obtained from C57BL/6J mice. The injected blastocysts were introduced into pseudopregnant fema...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.22.8927
更新日期:1989-11-01 00:00:00
abstract::Type 1A diabetes (T1D) is an autoimmune disorder the risk of which is increased by specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3) or DRB1*04-DQB1*0302 (DR4)]. The genotype associated with the highest risk for T1D is the DR3/4-DQ8 (DQ8 is DQA1*0301, DQB1*0302) heterozygous genotype. We determined HLA-DR and ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0606349103
更新日期:2006-09-19 00:00:00
abstract::Cultures were prepared of embryonic cells from Drosophila melanogaster. Neurons and myocytes differentiated in vitro from their respective stem cells. Electron microscopy showed that neuromuscular junctions formed where axons contacted myocytes. Electrical stimuli were applied to axons and these caused contractions of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.69.3.566
更新日期:1972-03-01 00:00:00
abstract::Thrombospondin, a 450-kDa multinodular glycoprotein with lectin-type activity, is found in human platelets, endothelial cells, fibroblasts, smooth muscle cells, monocytes, and granular pneumocytes. Thrombospondin interacts with heparin, fibrinogen, fibronectin, collagen, histidine-rich glycoprotein, and plasminogen. R...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.9.2904
更新日期:1986-05-01 00:00:00
abstract::Transcription in the human immunodeficiency virus type 1 (HIV-1) retrovirus is regulated by binding the viral Tat protein (trans-acting transcriptional activator) to the trans-activation response (TAR) RNA sequence. Here, vacuum UV circular dichroism (VUV-CD) is used to study the structure of TAR and its complex with ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.20.9734
更新日期:1992-10-15 00:00:00
abstract::Glucose, one of the most important nutrients for animals, acts as a regulatory signal that controls the secretion of hormones, such as insulin, by endocrine tissues. However, how organisms respond to extracellular glucose and how glucose controls nutrient homeostasis remain unknown. Here, we show that a putative Droso...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0807833105
更新日期:2008-10-07 00:00:00
abstract::In classical evolutionary theory, traits evolve because they facilitate organismal survival and/or reproduction. We discuss a different type of evolutionary mechanism that relies upon differential dispersal. Traits that enhance rates of dispersal inevitably accumulate at expanding range edges, and assortative mating b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1018989108
更新日期:2011-04-05 00:00:00
abstract::Mouse interferon preparations inhibited the multiplication of mouse leukemia L 1210 cells cultivated under steady-state conditions in a chemostat. The use of this sensitive and controlled system led to the detection of a rapid inhibition in the incorporation of (3-H)thymidine into cellular acid-precipitable material 2...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.6.2265
更新日期:1975-06-01 00:00:00
abstract::Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This protein...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.7.3173
更新日期:1978-07-01 00:00:00
abstract::Murine embryonic stem (ES) cells were infected with a retrovirus promoter trap vector, and clones expressing lacZ fusion genes (LacZ+) were isolated by fluorescence-activated cell sorting (FACS). Of 12 fusion genes tested, 1 was repressed when ES cells were allowed to differentiate in vitro. Two of three lacZ fusion g...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.15.6721
更新日期:1992-08-01 00:00:00
abstract::Animals are typically colonized by diverse bacterial symbionts, many of which are commensal and, in numerous cases, even essential for their host's proper development and growth. In exchange, the host must supply a sufficient array and quantity of nutrients to support the proliferation and persistence of its microbial...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.4.1818
更新日期:1998-02-17 00:00:00
abstract::Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain. This amyloid primarily contains amyloid-beta (Abeta), a 39- to 43-aa peptide derived from the proteolytic cleavage of the endogenous amyloid precursor protein. The 42-residue-length Abeta peptide (Abe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0901085106
更新日期:2009-03-24 00:00:00
abstract::RNA-dependent RNA polymerases (RdRps) of the Nidovirales (Coronaviridae, Arteriviridae, and 12 other families) are linked to an amino-terminal (N-terminal) domain, called NiRAN, in a nonstructural protein (nsp) that is released from polyprotein 1ab by the viral main protease (Mpro). Previously, self-GMPylation/UMPylat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2022310118
更新日期:2021-02-09 00:00:00
abstract::Many animals employ sex pheromones to find mating partners during their reproductive seasons. However, most sex pheromones of vertebrates remain to be identified. Over the past 20 years, steroids and prostaglandins have been identified as sex pheromones in several fishes. These pheromones are broadly termed "hormonal ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0604340103
更新日期:2006-10-17 00:00:00
abstract::Rivers around the world are being regulated by dams to accommodate the needs of a rapidly growing global population. These regulatory efforts usually oppose the natural tendency of rivers to flood, move sediment, and migrate. Although an economic benefit, river regulation has come at unforeseen and unevaluated cumulat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.22.11858
更新日期:2000-10-24 00:00:00
abstract::Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse muta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.112212199
更新日期:2002-05-28 00:00:00
abstract::A loss-of-function mutation in the APC gene initiates colorectal carcinogenesis. Although the molecular mechanism of tumor initiation is complex, several modifier genes have been identified using mouse models, including the ApcMin mouse. Among the familial adenomatous polyposis mouse lines carrying a truncation mutati...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705730104
更新日期:2007-11-13 00:00:00
abstract::In North America there are two generally recognized pathotypes (pathotypes 1 and 2) of the fungus Entomophaga grylli which show host-preferential infection of grasshopper subfamilies. Pathotype 3, discovered in Australia, has a broader grasshopper host range and was considered to be a good biocontrol agent. Between 19...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.2.918
更新日期:1996-01-23 00:00:00
abstract::Whether G protein-coupled receptors signal from endosomes to control important pathophysiological processes and are therapeutic targets is uncertain. We report that opioids from the inflamed colon activate δ-opioid receptors (DOPr) in endosomes of nociceptors. Biopsy samples of inflamed colonic mucosa from patients an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2000500117
更新日期:2020-06-30 00:00:00
abstract::This paper studies the cathodic corrosion of a spherical single crystal of platinum in an aqueous alkaline electrolyte, to map out the detailed facet dependence of the corrosion structures forming during this still largely unexplored electrochemical phenomenon. We find that anisotropic corrosion of the platinum electr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2017086117
更新日期:2020-12-22 00:00:00
abstract::To study the role of the interferon- (IFN) gammaR2 chain in IFN-gamma signaling and immune function, IFN-gammaR2-deficient mice have been generated and characterized. Cells derived from IFN-gammaR2 -/- mice are unable to activate either JAK/STAT signaling proteins or gene transcription in response to IFN-gamma. The la...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.14.8233
更新日期:1998-07-07 00:00:00
abstract::In Drosophila, Pumilio (Pum) is important for neuronal homeostasis as well as learning and memory. We have recently characterized a mammalian homolog of Pum, Pum2, which is found in discrete RNA-containing particles in the somatodendritic compartment of polarized neurons. In this study, we investigated the role of Pum...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0907128107
更新日期:2010-02-16 00:00:00
abstract::The status of the Archaea as one of the three primary Domains emphasizes the importance of understanding their molecular fundamentals. Basic transcription in the Archaea resembles eucaryal transcription. However, little is known about transcriptional regulation. We have taken an in vivo approach, using genetics to add...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.4.1316
更新日期:1997-02-18 00:00:00
abstract::This paper investigates quantitatively the characteristics of the local folding code. The overlapping four-residue fragments which make up the amino acid sequences of 114 proteins are divided into classes on the basis of the physical properties of their constituent amino acids. The distribution of structural types ass...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.2.644
更新日期:1993-01-15 00:00:00
abstract::The biosynthesis of beta-nerve growth factor (betaNGF) was studied in mouse submaxillary glands incubated with L-[(35)S]cystine. betaNGF was isolated from tissue extracts by the addition of antiserum against betaNGF and the washed immunoprecipitates were analyzed by sodium dodecyl sulfate gel electrophoresis. With sho...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.9.3647
更新日期:1977-09-01 00:00:00
abstract::A descriptive medium for the presentation of protein structure has been developed and used to evaluate the structure of the active site of bovine trypsin (EC 3.4.21.4). This technique, involving advanced computer graphics technology, permits the facile display of a representation of the molecular surface of proteins o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.11.5409
更新日期:1978-11-01 00:00:00
abstract::Uropathogenic Escherichia coli invade bladder epithelial cells (BECs) by direct entry into specialized cAMP regulated exocytic compartments. Remarkably, a significant number of these intracellular bacteria are subsequently expelled in a nonlytic and piecemeal fashion by infected BECs. Here, we report that expulsion of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0900527106
更新日期:2009-09-01 00:00:00
abstract::Cryopreservation is widely used to maintain backups of cells as it enables the semipermanent storage of cells. During the freezing process, ice crystals that are generated inside and outside the cells can lethally damage the cells. All conventional cryopreservation methods use at least one cryoprotective agent (CPA) t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1808645116
更新日期:2019-04-16 00:00:00
abstract::The mitogen-activated kinase activating death domain protein (MADD) that is differentially expressed in neoplastic vs. normal cells (DENN) was identified as a substrate for c-Jun N-terminal kinase 3, the first demonstration of such an activity for this stress-activated kinase that is predominantly expressed in the bra...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.5.2586
更新日期:1998-03-03 00:00:00