当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Germ-line variant of human NTH1 DNA glycosylase induces genomic instability and cellular transformation.

Germ-line variant of human NTH1 DNA glycosylase induces genomic instability and cellular transformation.

Abstract：

:Base excision repair (BER) removes at least 20,000 DNA lesions per human cell per day and is critical for the maintenance of genomic stability. We hypothesize that aberrant BER, resulting from mutations in BER genes, can lead to genomic instability and cancer. The first step in BER is catalyzed by DNA N-glycosylases. One of these, n(th) endonuclease III-like (NTH1), removes oxidized pyrimidines from DNA, including thymine glycol. The rs3087468 single nucleotide polymorphism of the NTH1 gene is a G-to-T base substitution that results in the NTH1 D239Y variant protein that occurs in ∼6.2% of the global population and is found in Europeans, Asians, and sub-Saharan Africans. In this study, we functionally characterize the effect of the D239Y variant expressed in immortal but nontransformed human and mouse mammary epithelial cells. We demonstrate that expression of the D239Y variant in cells also expressing wild-type NTH1 leads to genomic instability and cellular transformation as assessed by anchorage-independent growth, focus formation, invasion, and chromosomal aberrations. We also show that cells expressing the D239Y variant are sensitive to ionizing radiation and hydrogen peroxide and accumulate double strand breaks after treatment with these agents. The DNA damage response is also activated in D239Y-expressing cells. In combination, our data suggest that individuals possessing the D239Y variant are at risk for genomic instability and cancer.

journal_name

Proc Natl Acad Sci U S A

journal_title

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

authors

Galick HA,Kathe S,Liu M,Robey-Bond S,Kidane D,Wallace SS,Sweasy JB

doi

10.1073/pnas.1306752110

subject

Has Abstract

pub_date

2013-08-27 00:00:00

pages

14314-9

issue

35

eissn

0027-8424

issn

1091-6490

pii

1306752110

journal_volume

110

pub_type

杂志文章

相关文献

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA文献大全
  • High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine.

    abstract：:Unlike normal cells, malignant rat and two simian virus 40-transformed human cell lines can neither grow nor survive in B12-and folate-supplemented media in which methionine is replaced by homocysteine. Yet three lines of evidence indicate that the malignant and transformed cells synthesize large amounts of methionine...

    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.73.5.1523

    authors： Hoffman RM,Erbe RW

    更新日期：1976-05-01 00:00:00

  • Portraying the unique contribution of the default mode network to internally driven mnemonic processes.

    abstract：:Numerous neuroimaging studies have implicated default mode network (DMN) involvement in both internally driven processes and memory. Nevertheless, it is unclear whether memory operations reflect a particular case of internally driven processing or alternatively involve the DMN in a distinct manner, possibly depending ...

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

    pub_type： 临床试验,杂志文章

    doi：10.1073/pnas.1209888110

    authors： Shapira-Lichter I,Oren N,Jacob Y,Gruberger M,Hendler T

    更新日期：2013-03-26 00:00:00

  • Withdrawal of IL-7 induces Bax translocation from cytosol to mitochondria through a rise in intracellular pH.

    abstract：:IL-7 functions as a trophic factor during T lymphocyte development by a mechanism that is partly based on the induction of Bcl-2, which protects cells from apoptosis. Here we report a mechanism by which cytokine withdrawal activates the prodeath protein Bax. On loss of IL-7 in a dependent cell line, Bax protein transl...

    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.96.25.14476

    authors： Khaled AR,Kim K,Hofmeister R,Muegge K,Durum SK

    更新日期：1999-12-07 00:00:00

  • Inverse relationship between blood levels of high density lipoprotein subfraction 2 and magnitude of postprandial lipemia.

    abstract：:Triglyceridemic response to a standard oral fat meal was determined in 28 healthy subjects and related to the levels of several lipids, lipoproteins, and apolipoproteins in the post-absorptive plasma. A fatty test meal was administered orally, and postprandial plasma triglyceride levels were determined. In the fasting...

    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.80.5.1449

    authors： Patsch JR,Karlin JB,Scott LW,Smith LC,Gotto AM Jr

    更新日期：1983-03-01 00:00:00

  • Antibody response of mice to chemically induced tumors.

    abstract：:BALB/c mice immunized with syngeneic methylcholanthrene-induced fibrosarcomas did not have antibodies against the unique tumor-specific transplantation antigens, even though they were capable of rejecting a lethal dose of tumor cells. Endogenous murine leukemia virus antigens expressed by certain of the tumors did, ho...

    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.75.2.955

    authors： Brown JP,Klitzman JM,Hellström I,Nowinski RC,Hellström KE

    更新日期：1978-02-01 00:00:00

  • RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex.

    abstract：:Rapamycin is a potent immunosuppressant that blocks the G1/S transition in antigen-activated T cells and in yeast. The similar effects of rapamycin in animal cells and yeast suggest that the biochemical steps affected by rapamycin are conserved. Using a two-hybrid system we isolated mammalian clones that interact 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.91.26.12574

    authors： Chiu MI,Katz H,Berlin V

    更新日期：1994-12-20 00:00:00

  • Elastic free energy of anisotropic helical ribbons as metastable intermediates in the crystallization of cholesterol.

    abstract：:We report measurements of the geometrical structure and temporal evolution of metastable helical intermediates in the pathway for cholesterol crystallization in native and model biles. We find that the lecithin component in the bile can dramatically affect the kinetics along this pathway. We also present a 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.90.23.11341

    authors： Chung DS,Benedek GB,Konikoff FM,Donovan JM

    更新日期：1993-12-01 00:00:00

  • Triplet states in photosystem I of spinach chloroplasts and subchloroplast particles.

    abstract：:We report light-induced electron paramagnetic resonance triplet spectra from samples of chloroplasts or digitonin photosystem I particles that depend upon the dark redox state of the bound acceptors of photosystem I. If the reaction centers are prepared in the redox state P-700 A X- FdB-FdA-, then upon illumination at...

    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.76.10.5124

    authors： Frank HA,McLean MB,Sauer K

    更新日期：1979-10-01 00:00:00

  • Diversity enhances agricultural productivity via rhizosphere phosphorus facilitation on phosphorus-deficient soils.

    abstract：:Intercropping, which grows at least two crop species on the same pieces of land at the same time, can increase grain yields greatly. Legume-grass intercrops are known to overyield because of legume nitrogen fixation. However, many agricultural soils are deficient in phosphorus. Here we show that a new mechanism of ove...

    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.0704591104

    authors： Li L,Li SM,Sun JH,Zhou LL,Bao XG,Zhang HG,Zhang FS

    更新日期：2007-07-03 00:00:00

  • Ectopic expression of prion protein (PrP) in T lymphocytes or hepatocytes of PrP knockout mice is insufficient to sustain prion replication.

    abstract：:The cellular form of the Prion protein (PrPC) is necessary for prion replication in mice. To determine whether it is also sufficient, we expressed PrP under the control of various cell- or tissue-specific regulatory elements in PrP knockout mice. The interferon regulatory factor-1 promoter/Emu enhancer led to high PrP...

    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.96.7.3987

    authors： Raeber AJ,Sailer A,Hegyi I,Klein MA,Rülicke T,Fischer M,Brandner S,Aguzzi A,Weissmann C

    更新日期：1999-03-30 00:00:00

  • Protection of cardiac mitochondria by diazoxide and protein kinase C: implications for ischemic preconditioning.

    abstract：:Mitochondrial ATP-sensitive K (mitoK(ATP)) channels play a central role in protecting the heart from injury in ischemic preconditioning. In isolated mitochondria exposed to elevated extramitochondrial Ca, P(i), and anoxia to simulate ischemic conditions, the selective mitoK(ATP) channel agonist diazoxide (25-50 microM...

    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.052713199

    authors： Korge P,Honda HM,Weiss JN

    更新日期：2002-03-05 00:00:00

  • Global modulation of cellular transcription by human cytomegalovirus is initiated by viral glycoprotein B.

    abstract：:Human cytomegalovirus (HCMV) infection alters the expression of many cellular genes, including IFN-stimulated genes (ISGs) [Zhu, H., Cong, J.-P., Mamtora, G., Gingeras, T. & Shenk, T. (1998) Proc. Natl. Acad. Sci. USA 95, 14470-14475]. By using high-density cDNA microarrays, we show that the HCMV-regulated gene expres...

    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.121177598

    authors： Simmen KA,Singh J,Luukkonen BG,Lopper M,Bittner A,Miller NE,Jackson MR,Compton T,Früh K

    更新日期：2001-06-19 00:00:00

  • The genomic basis of trophic strategy in marine bacteria.

    abstract：:Many marine bacteria have evolved to grow optimally at either high (copiotrophic) or low (oligotrophic) nutrient concentrations, enabling different species to colonize distinct trophic habitats in the oceans. Here, we compare the genome sequences of two bacteria, Photobacterium angustum S14 and Sphingopyxis alaskensis...

    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.0903507106

    authors： Lauro FM,McDougald D,Thomas T,Williams TJ,Egan S,Rice S,DeMaere MZ,Ting L,Ertan H,Johnson J,Ferriera S,Lapidus A,Anderson I,Kyrpides N,Munk AC,Detter C,Han CS,Brown MV,Robb FT,Kjelleberg S,Cavicchioli R

    更新日期：2009-09-15 00:00:00

  • Human sleep consolidates allergic responses conditioned to the environmental context of an allergen exposure.

    abstract：:Allergies are highly prevalent, and allergic responses can be triggered even in the absence of allergens due to Pavlovian conditioning to a specific cue. Here we show in humans suffering from allergic rhinitis that merely reencountering the environmental context in which an allergen was administered a week earlier is ...

    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.1920564117

    authors： Besedovsky L,Benischke M,Fischer J,Yazdi AS,Born J

    更新日期：2020-05-19 00:00:00

  • Osmoregulatory changes in myo-inositol transport by renal cells.

    abstract：:Renal medullary cells contain high concentrations of myo-inositol, sorbitol, betaine, and glycerophosphocholine, whose levels vary with urinary osmolality. Accumulation of these "compatible" organic osmolytes is believed to help the cells osmoregulate in response to the high extracellular osmolality that occurs as par...

    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.86.15.6002

    authors： Nakanishi T,Turner RJ,Burg MB

    更新日期：1989-08-01 00:00:00

  • Export and stability of naturally intronless mRNAs require specific coding region sequences and the TREX mRNA export complex.

    abstract：:A great deal is known about the export of spliced mRNAs, but little is known about the export of mRNAs encoded by human cellular genes that naturally lack introns. Here, we investigated the requirements for export of three naturally intronless mRNAs (HSPB3, IFN-α1, and IFN-β1). Significantly, we found that all three m...

    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.1113076108

    authors： Lei H,Dias AP,Reed R

    更新日期：2011-11-01 00:00:00

  • Initiator tRNA may recognize more than the initiation codon in mRNA: a model for translational initiation.

    abstract：:A special methionine tRNA (tRNAi) is universally required to initiate translation. Amongst species a tRNAi structural conservation is most apparent in the anticodon and T arms of the molecule but extends into the variable loop and the 3' strand of the D stem. This suggested that they could share a similar ancestral or...

    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.82.14.4587

    authors： Ganoza MC,Marliere P,Kofoid EC,Louis BG

    更新日期：1985-07-01 00:00:00

  • Gcm protein degradation suppresses proliferation of glial progenitors.

    abstract：:Gliogenesis in animal development is spatiotemporally regulated so that correct numbers of glia are present to support various neuronal functions. During Drosophila embryonic development, the glial regulatory gene, glial cell missing/glial cell deficient (gcm/glide), promotes glial cell fate and differentiation. Here ...

    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.0808899106

    authors： Ho MS,Chen H,Chen M,Jacques C,Giangrande A,Chien CT

    更新日期：2009-04-21 00:00:00

  • Visualizing synaptic vesicle turnover and pool refilling driven by calcium nanodomains at presynaptic active zones of ribbon synapses.

    abstract：:Ribbon synapses of photoreceptor cells and second-order bipolar neurons in the retina are specialized to transmit graded signals that encode light intensity. Neurotransmitter release at ribbon synapses exhibits two kinetically distinct components, which serve different sensory functions. The faster component is deplet...

    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.1323962111

    authors： Vaithianathan T,Matthews G

    更新日期：2014-06-10 00:00:00

  • Evidence for adaptive radiation from a phylogenetic study of plant defenses.

    abstract：:One signature of adaptive radiation is a high level of trait change early during the diversification process and a plateau toward the end of the radiation. Although the study of the tempo of evolution has historically been the domain of paleontologists, recently developed phylogenetic tools allow for the rigorous exam...

    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.0904862106

    authors： Agrawal AA,Fishbein M,Halitschke R,Hastings AP,Rabosky DL,Rasmann S

    更新日期：2009-10-27 00:00:00

  • A normal beta-globin allele as a modifier gene ameliorating the severity of alpha-thalassemia in mice.

    abstract：:Thalassemia is a heritable human anemia caused by a variety of mutations that affect expression of the alpha- or the beta-chain of hemoglobin. The expressivity of the phenotype is likely to be influenced by unlinked modifying genes. Indeed, by using a mouse model of alpha-thalassemia, we find that its phenotype is str...

    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.96.11.6291

    authors： Leder A,Wiener E,Lee MJ,Wickramasinghe SN,Leder P

    更新日期：1999-05-25 00:00:00

  • Growth and viability of macrophages continuously stimulated to produce nitric oxide.

    abstract：:Deregulated production of nitric oxide (NO) has been implicated in the development of certain human diseases, including cancer. We sought to assess the damaging potential of NO produced under long-term conditions through the development of a suitable model cell culture system. In this study, we report that when murine...

    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.94.22.11875

    authors： Zhuang JC,Wogan GN

    更新日期：1997-10-28 00:00:00

  • Effects of early experience upon orientation sensitivity and binocularity of neurons in visual cortex of cats.

    abstract：:The class of neurons within the visual cortex of normal adult cats that has the smallest receptive fields (less than or equal to 2.25 degrees2) and that responds only to low rates of stimulus motion (less than or equal to 50 degrees / sec) responds preferentially to lines oriented about either the horizontal axis (+/-...

    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.74.3.1272

    authors： Leventhal AG,Hirsch HV

    更新日期：1977-03-01 00:00:00

  • The making of the Chandra X-Ray Observatory: the project scientist's perspective.

    abstract：:The history of the development of the Chandra X-Ray Observatory is reviewed from a personal perspective. This review is necessarily biased and limited by space because it attempts to cover a time span approaching five decades. ...

    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.0913067107

    authors： Weisskopf MC

    更新日期：2010-04-20 00:00:00

  • Calcium-dependent increase in adenosine 3',5'-monophosphate and induction of the acrosome reaction in guinea pig spermatozoa.

    abstract：:Experiments were designed to determine the interrelationship between cyclic AMP and Ca(2+) during the processes of sperm capacitation and the acrosome reaction. In minimal culture media containing pyruvate and lactate as substrates, guinea pig spermatozoa required a minimum of 1.0-1.5 hr to capacitate in the presence ...

    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.76.11.5699

    authors： Hyne RV,Garbers DL

    更新日期：1979-11-01 00:00:00

  • Ultrafast dynamics of hot carriers in a quasi-two-dimensional electron gas on InSe.

    abstract：:Two-dimensional electron gases (2DEGs) are at the base of current nanoelectronics because of their exceptional mobilities. Often the accumulation layer forms at polar interfaces with longitudinal optical (LO) modes. In most cases, the many-body screening of the quasi-2DEGs dramatically reduces the Fröhlich scattering ...

    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.2008282117

    authors： Chen Z,Sjakste J,Dong J,Taleb-Ibrahimi A,Rueff JP,Shukla A,Peretti J,Papalazarou E,Marsi M,Perfetti L

    更新日期：2020-09-08 00:00:00

  • Phylogeny of the genus Pistacia as determined from analysis of the chloroplast genome.

    abstract：:Classification within the genus Pistacia has been based on leaf morphology and geographical distribution. Molecular genetic tools (PCR amplification followed by restriction analysis of a 3.2-kb region of variable chloroplast DNA, and restriction fragment length polymorphism analysis of the Pistacia cpDNA with tobacco ...

    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.94.15.7987

    authors： Parfitt DE,Badenes ML

    更新日期：1997-07-22 00:00:00

  • Genomic drift and copy number variation of sensory receptor genes in humans.

    abstract：:The number of sensory receptor genes varies extensively among different mammalian species. This variation is believed to be caused partly by physiological requirements of animals and partly by genomic drift due to random duplication and deletion of genes. If the contribution of genomic drift is substantial, each speci...

    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.0709956104

    authors： Nozawa M,Kawahara Y,Nei M

    更新日期：2007-12-18 00:00:00

  • A plasma lipoprotein containing only apolipoprotein E and with gamma mobility on electrophoresis releases cholesterol from cells.

    abstract：:Previous studies have identified lipid-poor high density lipoproteins with electrophoretic pre-beta mobility as the initial acceptors of cell-derived cholesterol in human plasma. These lipoproteins contain apolipoprotein A-I (apo A-I) as their sole apolipoprotein. In the present study, incubation of human plasma 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.91.5.1834

    authors： Huang Y,von Eckardstein A,Wu S,Maeda N,Assmann G

    更新日期：1994-03-01 00:00:00

  • AgRP to Kiss1 neuron signaling links nutritional state and fertility.

    abstract：:Mammalian reproductive function depends upon a neuroendocrine circuit that evokes the pulsatile release of gonadotropin hormones (luteinizing hormone and follicle-stimulating hormone) from the pituitary. This reproductive circuit is sensitive to metabolic perturbations. When challenged with starvation, insufficient en...

    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.1621065114

    authors： Padilla SL,Qiu J,Nestor CC,Zhang C,Smith AW,Whiddon BB,Rønnekleiv OK,Kelly MJ,Palmiter RD

    更新日期：2017-02-28 00:00:00