Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro.

Abstract:

:The POT1 (protection of telomeres 1) protein binds the ssDNA overhangs at the ends of chromosomes in diverse eukaryotes. POT1 is essential for chromosome end-protection, as best demonstrated in fission yeast. In human cells, hPOT1 is also involved in telomere-length regulation. We now show that telomeric oligonucleotides, such as d[GGG(TTAGGG)(3)], which form intramolecular G-quadruplexes through Hoogsteen base-pairing, serve as only marginal primers for extension by recombinant human telomerase; telomerase stalls after every nucleotide addition. Addition of hPOT1 to the reaction restores the normal processive elongation pattern seen with primers that cannot form G-quadruplexes. hPOT1 does not act catalytically but, instead, forms a stoichiometric complex with the DNA, freeing its 3' tail. An antisense oligonucleotide, which base-pairs near the 5' end of the telomeric sequence, leaving a telomerase-extendable 3' tail, duplicates the effect of hPOT1 on activation of G-quadruplex primers. Thus, hPOT1 may function simply by trapping the unfolded forms of these telomeric primers in an equilibrium population. We propose an additional role for hPOT1 in telomere maintenance: disrupting G-quadruplex structures in telomeric DNA, thereby allowing proper elongation by telomerase.

authors

Zaug AJ,Podell ER,Cech TR

doi

10.1073/pnas.0504744102

keywords:

subject

Has Abstract

pub_date

2005-08-02 00:00:00

pages

10864-9

issue

31

eissn

0027-8424

issn

1091-6490

pii

0504744102

journal_volume

102

pub_type

杂志文章
  • A strategy for the identification of proteins targeted by thioredoxin.

    abstract::Thioredoxins are 12-kDa proteins functional in the regulation of cellular processes throughout the animal, plant, and microbial kingdoms. Growing evidence with seeds suggests that an h-type of thioredoxin, reduced by NADPH via NADP-thioredoxin reductase, reduces disulfide bonds of target proteins and thereby acts as 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.071041998

    authors: Yano H,Wong JH,Lee YM,Cho MJ,Buchanan BB

    更新日期:2001-04-10 00:00:00

  • Compound facial expressions of emotion.

    abstract::Understanding the different categories of facial expressions of emotion regularly used by us is essential to gain insights into human cognition and affect as well as for the design of computational models and perceptual interfaces. Past research on facial expressions of emotion has focused on the study of six basic ca...

    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.1322355111

    authors: Du S,Tao Y,Martinez AM

    更新日期:2014-04-15 00:00:00

  • Continuous 1.3-million-year record of East African hydroclimate, and implications for patterns of evolution and biodiversity.

    abstract::The transport of moisture in the tropics is a critical process for the global energy budget and on geologic timescales, has markedly influenced continental landscapes, migratory pathways, and biological evolution. Here we present a continuous, first-of-its-kind 1.3-My record of continental hydroclimate and lake-level ...

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

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1512864112

    authors: Lyons RP,Scholz CA,Cohen AS,King JW,Brown ET,Ivory SJ,Johnson TC,Deino AL,Reinthal PN,McGlue MM,Blome MW

    更新日期:2015-12-22 00:00:00

  • Hyperglycemia-induced teratogenesis is mediated by a functional deficiency of arachidonic acid.

    abstract::Congenital malformations now represent the largest single cause of mortality in the infant of the diabetic mother. The mechanism by which diabetes exerts its teratogenic effects is not known. This study evaluated whether arachidonic acid might be involved, a possibility raised by the role of arachidonic acid in palata...

    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.82.23.8227

    authors: Goldman AS,Baker L,Piddington R,Marx B,Herold R,Egler J

    更新日期:1985-12-01 00:00:00

  • Peroxisome biogenesis in the yeast Hansenula polymorpha is controlled by a complex set of interacting gene products.

    abstract::We have studied the genetic interactions between mutant alleles in 12 genes, designated PER1-PER12, which are essential for peroxisome biogenesis in the yeast Hansenula polymorpha. Recessive mutations in any of these genes determined three different morphological phenotypes: (i) complete absence of peroxisomes (Per-);...

    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.90.16.7470

    authors: Titorenko VI,Waterham HR,Cregg JM,Harder W,Veenhuis M

    更新日期:1993-08-15 00:00:00

  • Autogenous suppression of an opal mutation in the gene encoding peptide chain release factor 2.

    abstract::The peptide chain release factor 2 (RF2) gene, prfB, was cloned from Salmonella typhimurium by DNA hybridization using the Escherichia coli prfB probe. The nucleotide and amino acid sequences of prfB are 87.0% and 95.6% homologous between E. coli and S. typhimurium, respectively, including an in-frame premature UGA st...

    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.87.21.8432

    authors: Kawakami K,Nakamura Y

    更新日期:1990-11-01 00:00:00

  • Protection of the glutamate pool concentration in enteric bacteria.

    abstract::The central nitrogen metabolic circuit in enteric bacteria consists of three enzymes: glutamine synthetase, glutamate synthase (GOGAT), and glutamate dehydrogenase (GDH). With the carbon skeleton provided by 2-oxoglutarate, ammonia/ammonium (NH(4)(+)) is assimilated into two central nitrogen intermediates, glutamate 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.0703360104

    authors: Yan D

    更新日期:2007-05-29 00:00:00

  • Logistical feasibility and potential benefits of a population-wide passive-immunotherapy program during an influenza pandemic.

    abstract::Treatment strategies for severe cases of pandemic influenza have focused on antiviral therapies. In contrast, passive immunotherapy with convalescent blood products has received limited attention. We consider the hypothesis that a passive-immunotherapy program that collects plasma from a small percentage of recovered ...

    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.0911596107

    authors: Wu JT,Lee CK,Cowling BJ,Yuen KY

    更新日期:2010-02-16 00:00:00

  • Processing of precursors of 21S ribosomal RNA from yeast mitochondria.

    abstract::The transcription and processing of mitochondrial 21S rRNA in a petite strain of Saccharomyces cerevisiae has been examined by electron microscopic analysis of R-loop hybrids and by hybridization of labeled mitochondrial DNA probes to RNA transferred to diazobenzyloxymethyl paper. We have shown the presence of a large...

    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.77.3.1417

    authors: Merten S,Synenki RM,Locker J,Christianson T,Rabinowitz M

    更新日期:1980-03-01 00:00:00

  • Closely linked early and late histone H2B genes are differentially expressed after microinjection into sea urchin zygotes.

    abstract::An early and a late histone H2B gene from the sea urchin Stronglyocentrotus purpuratus were linked in a single plasmid and injected into the eggs of the sea urchin Lytechinus pictus. The levels of transcripts of injected early and late genes and of endogenous early genes were monitored during development by a ribonucl...

    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.85.2.507

    authors: Colin AM,Catlin TL,Kidson SH,Maxson R

    更新日期:1988-01-01 00:00:00

  • Sequences near the termini are required for transposition of the maize transposon Ac in transgenic tobacco plants.

    abstract::Deletion derivatives of the maize transposable element Activator (Ac) were constructed in vitro and inserted into a kanamycin resistance gene. These constructions were then introduced into tobacco protoplasts derived from plants previously transformed with Ac. The ability of each deletion derivative to excise was meas...

    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.86.23.9385

    authors: Coupland G,Plum C,Chatterjee S,Post A,Starlinger P

    更新日期:1989-12-01 00:00:00

  • Drosophila IRBP bZIP heterodimer binds P-element DNA and affects hybrid dysgenesis.

    abstract::In Drosophila, P-element transposition causes mutagenesis and genome instability during hybrid dysgenesis. The P-element 31-bp terminal inverted repeats (TIRs) contain sequences essential for transposase cleavage and have been implicated in DNA repair via protein-DNA interactions with cellular proteins. The identity 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.1613508113

    authors: Francis MJ,Roche S,Cho MJ,Beall E,Min B,Panganiban RP,Rio DC

    更新日期:2016-11-15 00:00:00

  • Brain-to-brain coupling during handholding is associated with pain reduction.

    abstract::The mechanisms underlying analgesia related to social touch are not clear. While recent research highlights the role of the empathy of the observer to pain relief in the target, the contribution of social interaction to analgesia is unknown. The current study examines brain-to-brain coupling during pain with interpers...

    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.1703643115

    authors: Goldstein P,Weissman-Fogel I,Dumas G,Shamay-Tsoory SG

    更新日期:2018-03-13 00:00:00

  • In vivo functional protein-protein interaction: nuclear targeted hsp90 shifts cytoplasmic steroid receptor mutants into the nucleus.

    abstract::In target tissue extracts, heat shock protein hsp90 has been found associated to all unliganded steroid receptors. Modulation of important functions of these receptors, including prevention of DNA binding and optimization of transcriptional activity, has been attributed to hsp90. However no unequivocal in vivo demonst...

    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.91.1.340

    authors: Kang KI,Devin J,Cadepond F,Jibard N,Guiochon-Mantel A,Baulieu EE,Catelli MG

    更新日期:1994-01-04 00:00:00

  • Antibody WN1 222-5 mimics Toll-like receptor 4 binding in the recognition of LPS.

    abstract::Escherichia coli infections, a leading cause of septic shock, remain a major threat to human health because of the fatal action to endotoxin (LPS). Therapeutic attempts to neutralize endotoxin currently focus on inhibiting the interaction of the toxic component lipid A with myeloid differentiating factor 2, which form...

    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.1209253109

    authors: Gomery K,Müller-Loennies S,Brooks CL,Brade L,Kosma P,Di Padova F,Brade H,Evans SV

    更新日期:2012-12-18 00:00:00

  • A general method for greatly improving the affinity of antibodies by using combinatorial libraries.

    abstract::Look-through mutagenesis (LTM) is a multidimensional mutagenesis method that simultaneously assesses and optimizes combinatorial mutations of selected amino acids. The process focuses on a precise distribution within one or more complementarity determining region (CDR) domains and explores the synergistic contribution...

    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.0503543102

    authors: Rajpal A,Beyaz N,Haber L,Cappuccilli G,Yee H,Bhatt RR,Takeuchi T,Lerner RA,Crea R

    更新日期:2005-06-14 00:00:00

  • Macropredatory ichthyosaur from the Middle Triassic and the origin of modern trophic networks.

    abstract::The biotic recovery from Earth's most severe extinction event at the Permian-Triassic boundary largely reestablished the preextinction structure of marine trophic networks, with marine reptiles assuming the predator roles. However, the highest trophic level of today's marine ecosystems, i.e., macropredatory tetrapods ...

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

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1216750110

    authors: Fröbisch NB,Fröbisch J,Sander PM,Schmitz L,Rieppel O

    更新日期:2013-01-22 00:00:00

  • Polarity of influenza and vesicular stomatitis virus maturation in MDCK cells: lack of a requirement for glycosylation of viral glycoproteins.

    abstract::We have investigated whether glycosylation of membrane glycoproteins is a determinant of the site of maturation of enveloped viruses in Madin-Darby canine kidney (MDCK) cells. In MDCK cell monolayers, vesicular stomatitis virus buds exclusively from the basal or lateral plasma membranes and contains a sialylated glyco...

    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.76.12.6430

    authors: Roth MG,Fitzpatrick JP,Compans RW

    更新日期:1979-12-01 00:00:00

  • Protein-binding dynamics imaged in a living cell.

    abstract::Historically, rate constants were determined in vitro and it was unknown whether they were valid for in vivo biological processes. Here, we bridge this gap by measuring binding dynamics between a pair of proteins in living HeLa cells. Binding of a β-lactamase to its protein inhibitor was initiated by microinjection 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.1112171109

    authors: Phillip Y,Kiss V,Schreiber G

    更新日期:2012-01-31 00:00:00

  • A localized differentiation-inducing-factor sink in the front of the Dictyostelium slug.

    abstract::Differentiation-inducing factor 1 [DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)-hexan-1-one] induces stalk cell differentiation during Dictyostelium development. It is present as a gradient in the multicellular slug, its lowest concentration being in the anterior. Here we demonstrate the existence of a locali...

    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.90.2.487

    authors: Kay RR,Large S,Traynor D,Nayler O

    更新日期:1993-01-15 00:00:00

  • Molecular definition of bovine argininosuccinate synthetase deficiency.

    abstract::Citrullinemia is an inborn error of metabolism due to deficiency of the urea cycle enzyme, argininosuccinate synthetase [L-citrulline:L-aspartate ligase (AMP-forming), EC 6.3.4.5]. The disease was first described in humans but was recently reported in dairy cattle in Australia. Here we report the nucleotide sequence 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.86.20.7947

    authors: Dennis JA,Healy PJ,Beaudet AL,O'Brien WE

    更新日期:1989-10-01 00:00:00

  • Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air.

    abstract::The influenza virus genes that confer efficient transmission of epidemic and pandemic strains in humans have not been identified. The rapid spread and severe disease caused by the 1918 influenza pandemic virus makes it an ideal virus to study the transmissibility of potentially pandemic influenza strains. Here, we use...

    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.0813172106

    authors: Van Hoeven N,Pappas C,Belser JA,Maines TR,Zeng H,García-Sastre A,Sasisekharan R,Katz JM,Tumpey TM

    更新日期:2009-03-03 00:00:00

  • Evidence from central Mexico supporting the Younger Dryas extraterrestrial impact hypothesis.

    abstract::We report the discovery in Lake Cuitzeo in central Mexico of a black, carbon-rich, lacustrine layer, containing nanodiamonds, microspherules, and other unusual materials that date to the early Younger Dryas and are interpreted to result from an extraterrestrial impact. These proxies were found in a 27-m-long core as p...

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

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1110614109

    authors: Israde-Alcántara I,Bischoff JL,Domínguez-Vázquez G,Li HC,DeCarli PS,Bunch TE,Wittke JH,Weaver JC,Firestone RB,West A,Kennett JP,Mercer C,Xie S,Richman EK,Kinzie CR,Wolbach WS

    更新日期:2012-03-27 00:00:00

  • Generation of a nicking enzyme that stimulates site-specific gene conversion from the I-AniI LAGLIDADG homing endonuclease.

    abstract::Homing endonucleases stimulate gene conversion by generating site-specific DNA double-strand breaks that are repaired by homologous recombination. These enzymes are potentially valuable tools for targeted gene correction and genome engineering. We have engineered a variant of the I-AniI homing endonuclease that nicks ...

    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.0810588106

    authors: McConnell Smith A,Takeuchi R,Pellenz S,Davis L,Maizels N,Monnat RJ Jr,Stoddard BL

    更新日期:2009-03-31 00:00:00

  • Role of excited electronic states in the high-pressure amorphization of benzene.

    abstract::High-pressure methods are increasingly used to produce new dense materials with unusual properties. Increasing efforts to understand the reaction mechanisms at the microscopic level, to set up and optimize synthetic approaches, are currently directed at carbon-based solids. A fundamental, but still unsolved, question ...

    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.0802269105

    authors: Citroni M,Bini R,Foggi P,Schettino V

    更新日期:2008-06-03 00:00:00

  • Low levels of deoxynucleotides in peripheral blood lymphocytes: a strategy to inhibit human immunodeficiency virus type 1 replication.

    abstract::Human immunodeficiency virus type 1 (HIV-1) viral DNA synthesis in quiescent and activated peripheral blood lymphocytes (PBLs) was studied. Incomplete viral DNA (previously demonstrated to be associated with HIV-1 virions) is carried by HIV-1 virions into quiescent and activated PBLs, contributing to the formation 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.90.19.8925

    authors: Gao WY,Cara A,Gallo RC,Lori F

    更新日期:1993-10-01 00:00:00

  • Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer.

    abstract::This article extends our previous quantitative analysis of the relationship between the dynamics of the primary structure of DNA and mutagenesis associated with single-strand lesions to an analysis of the production and processing of endogenous double-strand breaks (EDSBs) and to their implications for oncogenesis. 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.2135498100

    authors: Vilenchik MM,Knudson AG

    更新日期:2003-10-28 00:00:00

  • Functional expression of the Chlorella hexose transporter in Schizosaccharomyces pombe.

    abstract::Schizosaccharomyces pombe cells were transformed with an S. pombe expression vector containing a full-length cDNA of the Chlorella hexose transporter. The transformed cells accumulated 3-O-methylglucose up to 10-fold, whereas wild-type S. pombe and control transformants could only equilibrate this sugar analogue. In 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.87.20.7949

    authors: Sauer N,Caspari T,Klebl F,Tanner W

    更新日期:1990-10-01 00:00:00

  • Specific inactivation of two immunomodulatory SIGLEC genes during human evolution.

    abstract::Sialic acid-recognizing Ig-like lectins (Siglecs) are signaling receptors that modulate immune responses, and are targeted for interactions by certain pathogens. We describe two primate Siglecs that were rendered nonfunctional by single genetic events during hominin evolution after our common ancestor with the chimpan...

    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.1119459109

    authors: Wang X,Mitra N,Secundino I,Banda K,Cruz P,Padler-Karavani V,Verhagen A,Reid C,Lari M,Rizzi E,Balsamo C,Corti G,De Bellis G,Longo L,NISC Comparative Sequencing Program.,Beggs W,Caramelli D,Tishkoff SA,Hayakawa T,Gree

    更新日期:2012-06-19 00:00:00

  • Identification of Mycobacterium avium pathogenicity island important for macrophage and amoeba infection.

    abstract::The ability to infect macrophages is a common characteristic shared among many mycobacterial species. Mycobacterium avium, Mycobacterium tuberculosis, and Mycobacterium kansasii enter macrophages, using the complement receptors CR1, CR3, CR4, and the mannose receptor. To identify M. avium genes and host cell pathways ...

    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.0610746104

    authors: Danelishvili L,Wu M,Stang B,Harriff M,Cirillo SL,Cirillo JD,Bildfell R,Arbogast B,Bermudez LE

    更新日期:2007-06-26 00:00:00