Fidelity of a human cell DNA replication complex.

Abstract:

:We have measured the fidelity of bidirectional, semiconservative DNA synthesis by a human DNA replication complex in vitro. Replication was performed by extracts of HeLa cells in the presence of simian virus 40 (SV40) large tumor antigen by using a double-stranded phage M13mp2 DNA template containing the SV40 origin of replication and either of two different target sequences for scoring mutations in the lacZ alpha-complementation gene, which encodes the alpha region (specifying the amino-terminal portion) of beta-galactosidase. Replicative synthesis was substantially more accurate than synthesis by the human DNA polymerase alpha-DNA primase complex purified from HeLa cell extracts by immunoaffinity chromatography, suggesting that additional factors or activities in the extract may increase fidelity during bidirectional replication. However, by using a sensitive opal codon reversion assay, single-base substitution errors were readily detected in the replication products at frequencies significantly higher than estimated spontaneous mutation rates in vivo. These data suggest that additional fidelity factors may be present during chromosomal replication in vivo and/or that the fidelity of replication alone does not account for the low spontaneous mutation rates in eukaryotes.

authors

Roberts JD,Kunkel TA

doi

10.1073/pnas.85.19.7064

subject

Has Abstract

pub_date

1988-10-01 00:00:00

pages

7064-8

issue

19

eissn

0027-8424

issn

1091-6490

journal_volume

85

pub_type

杂志文章
  • Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK.

    abstract::Monoclonal antibodies can block cellular interactions that negatively regulate T-cell immune responses, such as CD80/CTLA-4 and PD-1/PD1-L, amplifying preexisting immunity and thereby evoking antitumor immune responses. Ibrutinib, an approved therapy for B-cell malignancies, is a covalent inhibitor of BTK, a member 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.1500712112

    authors: Sagiv-Barfi I,Kohrt HE,Czerwinski DK,Ng PP,Chang BY,Levy R

    更新日期:2015-03-03 00:00:00

  • Local molecular field theory for effective attractions between like charged objects in systems with strong Coulomb interactions.

    abstract::Strong, short-ranged positional correlations involving counterions can induce a net attractive force between negatively charged strands of DNA and lead to the formation of ion pairs in dilute ionic solutions. However, the long range of the Coulomb interactions impedes the development of a simple local picture. We addr...

    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.0600282103

    authors: Chen YG,Weeks JD

    更新日期:2006-05-16 00:00:00

  • Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2.

    abstract::Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, employs two key host proteins to gain entry and replicate within cells, angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2). TMPRSS2 was first characterized as an androgen...

    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.2021450118

    authors: Qiao Y,Wang XM,Mannan R,Pitchiaya S,Zhang Y,Wotring JW,Xiao L,Robinson DR,Wu YM,Tien JC,Cao X,Simko SA,Apel IJ,Bawa P,Kregel S,Narayanan SP,Raskind G,Ellison SJ,Parolia A,Zelenka-Wang S,McMurry L,Su F,Wang R,

    更新日期:2020-12-11 00:00:00

  • Escherichia coli genes regulated by cell-to-cell signaling.

    abstract::Utilizing the bicistronic reporter transposon mini-Tn5 lacZ-tet/1, we have identified lacZ fusions to four Escherichia coli genes/operons that are strongly activated by the accumulation of self-produced extracellular signals. These fusions were designated cma9, cma48, cma113, and cma114 for conditioned medium activate...

    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.96.8.4610

    authors: Baca-DeLancey RR,South MM,Ding X,Rather PN

    更新日期:1999-04-13 00:00:00

  • Selective blockage of initiation of host protein synthesis in RNA-virus-infected cells.

    abstract::Poliovirus mRNA and mRNA transcribed from vesicular stomatitis virus and reovirus genomes efficiently direct protein synthesis in vivo under experimental conditions where the initiation of host protein synthesis is selectively blocked. The selective blockage of host peptide chain initiation after exposure to hypertoni...

    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.72.4.1258

    authors: Nuss DL,Oppermann H,Koch G

    更新日期:1975-04-01 00:00:00

  • Tuning environmental timescales to evolve and maintain generalists.

    abstract::Natural environments can present diverse challenges, but some genotypes remain fit across many environments. Such "generalists" can be hard to evolve, outcompeted by specialists fitter in any particular environment. Here, inspired by the search for broadly neutralizing antibodies during B cell affinity maturation, 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.1914586117

    authors: Sachdeva V,Husain K,Sheng J,Wang S,Murugan A

    更新日期:2020-06-09 00:00:00

  • Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt+ NIK+ signalosome on Rab5+ endosomes.

    abstract::Complement membrane attack complexes (MACs) promote inflammatory functions in endothelial cells (ECs) by stabilizing NF-κB-inducing kinase (NIK) and activating noncanonical NF-κB signaling. Here we report a novel endosome-based signaling complex induced by MACs to stabilize NIK. We found that, in contrast to cytokine-...

    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.1503535112

    authors: Jane-wit D,Surovtseva YV,Qin L,Li G,Liu R,Clark P,Manes TD,Wang C,Kashgarian M,Kirkiles-Smith NC,Tellides G,Pober JS

    更新日期:2015-08-04 00:00:00

  • Structural organization of a filamentous influenza A virus.

    abstract::Influenza is a lipid-enveloped, pleomorphic virus. We combine electron cryotomography and analysis of images of frozen-hydrated virions to determine the structural organization of filamentous influenza A virus. Influenza A/Udorn/72 virions are capsule-shaped or filamentous particles of highly uniform diameter. We show...

    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.1002123107

    authors: Calder LJ,Wasilewski S,Berriman JA,Rosenthal PB

    更新日期:2010-06-08 00:00:00

  • Endogenous oxidative damage of deoxycytidine in DNA.

    abstract::Three major oxidation products of 2'-deoxycytidine (dC)--5-hydroxy-2'-deoxycytidine (oh5dC), 5-hydroxy-2'-deoxyuridine (oh5dU), and 5,6-dihydroxy-5,6-dihydro-2'-deoxyuridine (dUg)--were analyzed from enzymatically hydrolyzed DNA with reversed-phase high-performance liquid chromatography coupled to electrochemical dete...

    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.89.8.3380

    authors: Wagner JR,Hu CC,Ames BN

    更新日期:1992-04-15 00:00:00

  • Segregation of leading-edge and uropod components into specific lipid rafts during T cell polarization.

    abstract::Redistribution of specialized molecules in migrating cells develops asymmetry between two opposite cell poles, the leading edge and the uropod. We show that acquisition of a motile phenotype in T lymphocytes results in the asymmetric redistribution of ganglioside GM3- and GM1-enriched raft domains to the leading edge ...

    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.171160298

    authors: Gómez-Móuton C,Abad JL,Mira E,Lacalle RA,Gallardo E,Jiménez-Baranda S,Illa I,Bernad A,Mañes S,Martínez-A C

    更新日期:2001-08-14 00:00:00

  • The impact of Miocene atmospheric carbon dioxide fluctuations on climate and the evolution of terrestrial ecosystems.

    abstract::The Miocene is characterized by a series of key climatic events that led to the founding of the late Cenozoic icehouse mode and the dawn of modern biota. The processes that caused these developments, and particularly the role of atmospheric CO2 as a forcing factor, are poorly understood. Here we present a CO2 record 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.0708588105

    authors: Kürschner WM,Kvacek Z,Dilcher DL

    更新日期:2008-01-15 00:00:00

  • rRNA complementarity within mRNAs: a possible basis for mRNA-ribosome interactions and translational control.

    abstract::Our recent demonstration that many eukaryotic mRNAs contain sequences complementary to rRNA led to the hypothesis that these sequences might mediate specific interactions between mRNAs and ribosomes and thereby affect translation. In the present experiments, the ability of complementary sequences to bind to rRNA was i...

    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.95.21.12238

    authors: Tranque P,Hu MC,Edelman GM,Mauro VP

    更新日期:1998-10-13 00:00:00

  • Probing the evolution of appendage specialization by Hox gene misexpression in an emerging model crustacean.

    abstract::Changes in the expression of Hox genes have been widely linked to the evolution of animal body plans, but functional demonstrations of this relationship have been impeded by the lack of suitable model organisms. A classic case study involves the repeated evolution of specialized feeding appendages, called maxillipeds,...

    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.0902804106

    authors: Pavlopoulos A,Kontarakis Z,Liubicich DM,Serano JM,Akam M,Patel NH,Averof M

    更新日期:2009-08-18 00:00:00

  • Causes and consequences of asymmetric lateral plume flow during South Atlantic rifting.

    abstract::Volcanic rifted margins are typically associated with a thick magmatic layer of seaward dipping reflectors and anomalous regional uplift. This is conventionally interpreted as due to melting of an arriving mantle plume head at the onset of rifting. However, seaward dipping reflectors and uplift are sometimes asymmetri...

    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.2012246117

    authors: Morgan JP,Taramón JM,Araujo M,Hasenclever J,Perez-Gussinye M

    更新日期:2020-11-10 00:00:00

  • Effects of methionine on the cytoplasmic distribution of actin and tubulin during neural tube closure in rat embryos.

    abstract::Research has previously shown that, without methionine supplements, neural tube proteins of rat embryos cultured on bovine sera were hypomethylated and neural tubes failed to close. In the present study, to identify the proteins that became methylated during neurulation, rat embryos were first cultured on methionine-d...

    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.94.2.543

    authors: Moephuli SR,Klein NW,Baldwin MT,Krider HM

    更新日期:1997-01-21 00:00:00

  • Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration.

    abstract::Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific de-ubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebella...

    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.1222732110

    authors: Bilguvar K,Tyagi NK,Ozkara C,Tuysuz B,Bakircioglu M,Choi M,Delil S,Caglayan AO,Baranoski JF,Erturk O,Yalcinkaya C,Karacorlu M,Dincer A,Johnson MH,Mane S,Chandra SS,Louvi A,Boggon TJ,Lifton RP,Horwich AL,Gunel M

    更新日期:2013-02-26 00:00:00

  • Poly(ADP-ribose) glycohydrolase mediates oxidative and excitotoxic neuronal death.

    abstract::Excessive activation of poly(ADP-ribose) polymerase 1 (PARP1) leads to NAD(+) depletion and cell death during ischemia and other conditions that generate extensive DNA damage. When activated by DNA strand breaks, PARP1 uses NAD(+) as substrate to form ADP-ribose polymers on specific acceptor proteins. These polymers a...

    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.211202598

    authors: Ying W,Sevigny MB,Chen Y,Swanson RA

    更新日期:2001-10-09 00:00:00

  • Overlapping roles and asymmetrical cross-regulation of the USF proteins in mice.

    abstract::USF1 and USF2 are ubiquitously expressed transcription factors implicated as antagonists of the c-Myc protooncoprotein in the control of cellular proliferation. To determine the biological role of the USF proteins, mutant mice were generated by homologous recombination in embryonic stem cells. USF1-null mice were viab...

    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.95.7.3758

    authors: Sirito M,Lin Q,Deng JM,Behringer RR,Sawadogo M

    更新日期:1998-03-31 00:00:00

  • Macrophage activation: dissociation of cytotoxic activity from Ia-A antigen expression.

    abstract::Peritoneal macrophages were obtained from DBA/2 mice that were untreated or after the injection of bacillus Calmette-Guerin (BCG), thioglycollate broth, proteose-peptone broth, or gamma-irradiated P-815 tumor cells. These macrophages were "activated" to become cytotoxic for a fibroblast cell line (L 929) by the additi...

    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.80.7.2031

    authors: Blumenthal EJ,Roberts WK,Vasil A,Talmage DW

    更新日期:1983-04-01 00:00:00

  • COST1 regulates autophagy to control plant drought tolerance.

    abstract::Plants balance their competing requirements for growth and stress tolerance via a sophisticated regulatory circuitry that controls responses to the external environments. We have identified a plant-specific gene, COST1 (constitutively stressed 1), that is required for normal plant growth but negatively regulates droug...

    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.1918539117

    authors: Bao Y,Song WM,Wang P,Yu X,Li B,Jiang C,Shiu SH,Zhang H,Bassham DC

    更新日期:2020-03-31 00:00:00

  • T lymphocyte response to H-2 mutants: cytotoxic effectors are Ly-1+2+.

    abstract::The lymphocyte differentiation (Ly) antigen phenotype of cytotoxic effector T cells specific for H-2 mutant alloantigens was determined. Cytotoxic effectors generated in primary mixed lymphocyte culture and specific for H-2Kba and H-2Dda alloantigens are sensitive to both anti-Ly-1 and anti-Ly-2 serum plus complement....

    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.76.7.3455

    authors: Wettstein PJ,Bailey DW,Mobraaten LE,Klein J,Frelinger JA

    更新日期:1979-07-01 00:00:00

  • Phylogeny from function: evidence from the molecular fossil record that tRNA originated in replication, not translation.

    abstract::We propose a phylogeny for the evolution of tRNA that is based on the ubiquity and conservation of tRNA-like structures in the replication of contemporary genomes. This phylogeny is unique in suggesting that the function of tRNA in replication dates back to the very beginnings of life on earth, before the advent of te...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.91.15.6729

    authors: Maizels N,Weiner AM

    更新日期:1994-07-19 00:00:00

  • Growth, metabolic partitioning, and the size of microorganisms.

    abstract::Population growth rate is a fundamental ecological and evolutionary characteristic of living organisms, but individuals must balance the metabolism devoted to biosynthesis and reproduction against the maintenance of existing structure and other functionality. Here we present a mathematical model that relates metabolic...

    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.1115585109

    authors: Kempes CP,Dutkiewicz S,Follows MJ

    更新日期:2012-01-10 00:00:00

  • Activity-dormancy transition in the cambial meristem involves stage-specific modulation of auxin response in hybrid aspen.

    abstract::The molecular basis of short-day-induced growth cessation and dormancy in the meristems of perennial plants (e.g., forest trees growing in temperate and high-latitude regions) is poorly understood. Using global transcript profiling, we show distinct stage-specific alterations in auxin responsiveness of the transcripto...

    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.1011506108

    authors: Baba K,Karlberg A,Schmidt J,Schrader J,Hvidsten TR,Bako L,Bhalerao RP

    更新日期:2011-02-22 00:00:00

  • A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCgamma1 activation and angiogenesis.

    abstract::Activation of phospholipase Cgamma1 (PLCgamma1) by vascular endothelial growth factor receptor-2 (VEGFR-2) in endothelial cells in part is responsible for angiogenesis in vivo. The cellular mechanisms exerting negative control over PLCgamma1 activation, however, remain unaddressed. Here by using in vitro and in vivo 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.0700809104

    authors: Singh AJ,Meyer RD,Navruzbekov G,Shelke R,Duan L,Band H,Leeman SE,Rahimi N

    更新日期:2007-03-27 00:00:00

  • Amplification and deregulation of MYC following Epstein-Barr virus infection of a human B-cell line.

    abstract::In Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) the role of EBV in the translocation and deregulation of the MYC oncogene remains unknown. By utilizing an EBV-negative BL (BJAB) and several EBV-positive sublines derived from it by in vitro infection, it was possible to show that the presence of the virus wa...

    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.84.16.5838

    authors: Lacy J,Summers WP,Watson M,Glazer PM,Summers WC

    更新日期:1987-08-01 00:00:00

  • Hydrophobicity, hydrophilicity, and the radial and orientational distributions of residues in native proteins.

    abstract::The radial distributions of the Calpha and side-chain atoms in a sample of 13 native proteins have been examined. It is found that there are substantial differences in behavior between different atoms of the same amino acid. In particular, the Calpha atoms of polar residues show no particular preference for being far ...

    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.74.12.5248

    authors: Rackovsky S,Scheraga HA

    更新日期:1977-12-01 00:00:00

  • Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation.

    abstract::Delayed implantation (embryonic diapause) occurs when the embryo at the blastocyst stage achieves a state of suspended animation. During this period, blastocyst growth is very slow, with minimal or no cell division. Nearly 100 mammals in seven different orders undergo delayed implantation, but the underlying molecular...

    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.0402597101

    authors: Hamatani T,Daikoku T,Wang H,Matsumoto H,Carter MG,Ko MS,Dey SK

    更新日期:2004-07-13 00:00:00

  • Insulin release, insulin sensitivity, and glucose intolerance.

    abstract::Groups of subjects with different degrees of glucose intolerance were examined in order to determine, first, the capacity of the beta cells to release insulin upon glucose stimulation and, second, sensitivity to insulin. The groups were selected on the basis of fasting blood glucose value and tolerances to oral and in...

    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.77.12.7425

    authors: Efendić S,Wajngot A,Cerasi E,Luft R

    更新日期:1980-12-01 00:00:00

  • Tension responses to rapid pressure release in glycerinated rabbit muscle fibers.

    abstract::We have previously shown that the isometric tension of a fully calcium-activated skinned rabbit psoas muscle fiber is reversibly depressed by increased hydrostatic pressure. We report here the characterization of tension transients induced by a rapid (less than 1-ms) release of increased pressure at 12 degrees C. The ...

    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.88.16.7323

    authors: Fortune NS,Geeves MA,Ranatunga KW

    更新日期:1991-08-15 00:00:00