Abstract:
:High-resolution crystal structures of editing complexes of both duplex and single-stranded DNA bound to Escherichia coli DNA polymerase I large fragment (Klenow fragment) show four nucleotides of single-stranded DNA bound to the 3'-5' exonuclease active site and extending toward the polymerase active site. Melting of the duplex DNA by the protein is stabilized by hydrophobic interactions between Phe-473, Leu-361, and His-666 and the last three bases at the 3' terminus. Two divalent metal ions interacting with the phosphodiester to be hydrolyzed are proposed to catalyze the exonuclease reaction by a mechanism that may be related to mechanisms of other enzymes that catalyze phospho-group transfer including RNA enzymes. We suggest that the editing active site competes with the polymerase active site some 30 A away for the newly formed 3' terminus. Since a 3' terminal mismatched base pair favors the melting of duplex DNA, its binding and excision at the editing exonuclease site that binds single-stranded DNA is enhanced.
journal_name
Proc Natl Acad Sci U S Aauthors
Freemont PS,Friedman JM,Beese LS,Sanderson MR,Steitz TAdoi
10.1073/pnas.85.23.8924subject
Has Abstractpub_date
1988-12-01 00:00:00pages
8924-8issue
23eissn
0027-8424issn
1091-6490journal_volume
85pub_type
杂志文章abstract::Male white Swiss mice that had previously been made aggressive by several weeks of individual housing were allowed to fight for 5 to 10 minutes each day for 5, 10, or 14 consecutive days; fighting caused a marked enlargement of their adrenals, spleens, and hearts, and a large increase in adrenal catecholamines; brain ...
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.64.1.100
更新日期:1969-09-01 00:00:00
abstract::Fluids may store and manipulate information, enabling complex applications ranging from digital logic gates to algorithmic self-assembly. While controllable hydrodynamic chaos has previously been observed in viscous fluids and harnessed for efficient mixing, its application to the manipulation of digital information h...
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.1721852115
更新日期:2018-05-08 00:00:00
abstract::RNA molecules that bind a transition state analog for a Diels-Alder reaction (Kd = 0.35 +/- 0.05 mM) were isolated from a starting pool of approximately 10(14) sequences by affinity chromatography. After the initial rise and plateau of the amount of RNA that eluted with soluble analog, a step gradient elution was used...
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.91.26.13028
更新日期:1994-12-20 00:00:00
abstract::Photoreceptors of the Xenopus laevis retina are the site of a circadian clock. As part of a differential display screen for rhythmic gene products in this system, we have identified a photoreceptor-specific mRNA expressed in peak abundance at night. cDNA cloning revealed an open reading frame encoding a putative 388 a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 评论,杂志文章
doi:10.1073/pnas.93.25.14884
更新日期:1996-12-10 00:00:00
abstract::Populations of isogenic embryonic stem cells or clonal bacteria often exhibit extensive phenotypic heterogeneity that arises from intrinsic stochastic dynamics of cells. The phenotypic state of a cell can be transmitted epigenetically in cell division, leading to correlations in the states of cells related by descent....
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.1504407112
更新日期:2015-05-05 00:00:00
abstract::Observations with the image tube scanner at the Shane 3-m telescope are combined with data obtained with the International Ultraviolet Explorer to assess the spectrum of the remarkable high-excitation planetary nebula NGC 6537. We have analyzed the spectrum of this nitrogen-rich object with the aid of the theoretical ...
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.82.8.2202
更新日期:1985-04-01 00:00:00
abstract::A peptide containing 31 amino acids with inhibin-like activity has been synthesized by the solid-phase method. The synthetic product was shown to be homogeneous in high-performance liquid chromatography and paper electrophoresis. In the mouse pituitary incubation system, the follitropin-suppressing activity of the syn...
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.81.17.5399
更新日期:1984-09-01 00:00:00
abstract::Total nuclear proteins extracted from cell lines representing various stages of differentiation of mouse B lymphocytes were studied by computer analysis of two-dimensional gels. Of the 1438 spots present on the gels, 55 varied significantly in intensity during differentiation. The variations occurred most often in ste...
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.88.5.1830
更新日期:1991-03-01 00:00:00
abstract::It is a well known fact that stirring keeps particles suspended in fluids. This is apparent, for instance, when shaking medicine flasks, when agitating tea deposits in a mug, or when heavy winds fill the air with dust particles. The commonplace nature of such observations makes it easy to accept that this feature will...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0401539101
更新日期:2004-12-21 00:00:00
abstract::Telomerase is a special reverse transcriptase that extends one strand of the telomere repeat by using a template embedded in an RNA subunit. Like other polymerases, telomerase is believed to use a pair of divalent metal ions (coordinated by a triad of aspartic acid residues) for catalyzing nucleotide addition. Here we...
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.0502252102
更新日期:2005-07-12 00:00:00
abstract::Specific rabbit antisera against purified bovine pituitary carboxypeptidase processing enzyme (which has also been referred to as "enkephalin convertase") have been prepared and characterized. The antisera recognized both the purified soluble and the membrane-bound forms of the enzyme with equal affinity, suggesting 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.82.14.4745
更新日期:1985-07-01 00:00:00
abstract::Germ-line mutations of tumor suppressor genes confer strong predisposition to tumor formation. In the rat, a form of dominantly inherited renal carcinoma (RC) results in multiple chromophobe cell tumors that resemble the human disease, and heterozygous carriers (RC/+) are highly susceptible to environmental agents (ra...
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.90.17.8038
更新日期:1993-09-01 00:00:00
abstract::How genome divergence eventually leads to speciation is a topic of prime evolutionary interest. Genomic islands of elevated divergence are frequently reported between diverging lineages, and their size is expected to increase with time and gene flow under the speciation-with-gene-flow model. However, such islands can ...
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.1713288114
更新日期:2018-01-09 00:00:00
abstract::Many "workers" in north temperate colonies of the eusocial paper wasp Polistes fuscatus disappear within a few days of eclosion. We provide evidence that these females are pursuing an alternative reproductive strategy, i.e., dispersing to overwinter and become nest foundresses the following spring, instead of helping ...
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.95.23.13737
更新日期:1998-11-10 00:00:00
abstract::The p53 tumor suppressor protein and the MDM2 oncoprotein form a feedback-control loop that up-regulates cellular MDM2 production, blocks p53 activity, and promotes p53 decay. tsg101 was discovered as a gene whose deficiency results in neoplastic transformation of NIH 3T3 cells and the ability to generate metastatic 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.98.4.1619
更新日期:2001-02-13 00:00:00
abstract::Both laboratory and field data suggest that people punish noncooperators even in one-shot interactions. Although such "altruistic punishment" may explain the high levels of cooperation in human societies, it creates an evolutionary puzzle: existing models suggest that altruistic cooperation among nonrelatives is evolu...
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.0630443100
更新日期:2003-03-18 00:00:00
abstract::It had been shown previously that the heat-stable polypeptide of the ATP-dependent proteolytic system of reticulocytes, designated APF-1, forms covalent conjugates with protein substrates in an ATP-requiring process. We now describe an enzyme that carries out the activation by ATP of the polypeptide with pyrophosphate...
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.78.2.761
更新日期:1981-02-01 00:00:00
abstract::Model organism studies have demonstrated that cell fate specification decisions play an important role in normal brain development. Their role in human neurodevelopmental disorders, however, is poorly understood, with very few examples described. The cerebellum is an excellent system to study mechanisms of cell fate s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2014-04-29 00:00:00
abstract::Interbacterial interaction pathways play an important role in defining the structure and complexity of bacterial associations. A quantitative description of such pathways offers promise for understanding the forces that contribute to community composition. We developed time-lapse fluorescence microscopy methods for qu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2012-11-27 00:00:00
abstract::The catalytic generation of chiral ester enolate equivalents from α,β-unsaturated aldehydes with chiral N-hetereocyclic carbene catalysts makes possible highly enantioselective hetero-Diels-Alder reactions. The reactions proceed under simple, mild conditions with both aliphatic and aromatic substituted enals as substr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2010-11-30 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1996-02-06 00:00:00
abstract::Subtractive library construction and differential screening were used to identify a cDNA for a cell type-specific immediate early gene induced in rat PC12 pheochromocytoma cells. Sequencing identified the protein product of this gene as rat synaptotagmin IV (SytIV). Synaptotagmins are synaptic vesicle proteins thought...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1995-03-14 00:00:00
abstract::Mitochondrial function and ambulatory activity were monitored after feeding old rats acetyl-L-carnitine (ALCAR). Young (3-5 mo) and old (22-28 mo) rats were given a 1.5% (wt/vol) solution of ALCAR in their drinking water for 1 mo, were sacrificed, and their liver parenchymal cells were isolated. ALCAR supplementation ...
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.95.16.9562
更新日期:1998-08-04 00:00:00
abstract::Current drug discovery efforts focus on identifying lead compounds acting on a molecular target associated with an established pathological state. Concerted molecular changes that occur in specific cell types during disease progression have generally not been identified. Here, we used constellation pharmacology to inv...
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.1922618117
更新日期:2020-10-20 00:00:00
abstract::Genetic manipulation of the alpha(2A)-adrenergic receptor (alpha(2A)-AR) in mice has revealed the role of this subtype in numerous responses, including agonist-induced hypotension and sedation. Unexpectedly, alpha(2)-agonist treatment of mice heterozygous for the alpha(2A)-AR (alpha(2A)-AR(+/-)) lowers blood pressure ...
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.122368499
更新日期:2002-09-17 00:00:00
abstract::A model is presented for age-specific selection on the genotypes in a population. Each genotype is assigned a life table that specifies the viability and fecundity of its age classes. Breeding and reproduction occur at regular intervals, and generations overlap. Examples were generated on a digital computer. Gene freq...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.66.3.780
更新日期:1970-07-01 00:00:00
abstract::Refinement of neural circuits in the mammalian cerebral cortex shapes brain function during development and in the adult. However, the signaling mechanisms underlying the synapse-specific shrinkage and loss of spiny synapses when neural circuits are remodeled remain poorly defined. Here, we show that low-frequency glu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2013-01-22 00:00:00
abstract::The N,N'-diacetyllactosediamine (lacdiNAc) pathway of complex-type oligosaccharide synthesis is controlled by a UDP-GalNAc:GlcNAc beta-R beta 1-->4-N-acetylgalac-tesaminyltransferase (beta 4-GalNAcT) that acts analogously to the common UDP-Gal:GlcNAc beta-R beta 1-->4-galactosyltransferase (beta 4-GalT). LacdiNAc-base...
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.93.19.10111
更新日期:1996-09-17 00:00:00
abstract::A climate/vegetation model simulates episodic wetter and drier periods at the 21,000-y precession period in eastern North Africa, the Arabian Peninsula, and the Levant over the past 140,000 y. Large orbitally forced wet/dry extremes occur during interglacial time, ∼130 to 80 ka, and conditions between these two extrem...
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.1917673117
更新日期:2020-02-04 00:00:00
abstract::New data are reported on the influence of size on the velocity threshold for real movement. As the length of a narrow stimulus object increases, width remaining constant, the velocity threshold also increases. These findings are discussed in relation to some psychophysical experiments on contrast and some physiologica...
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.65.3.516
更新日期:1970-03-01 00:00:00