Alkylpurine-DNA-N-glycosylase knockout mice show increased susceptibility to induction of mutations by methyl methanesulfonate.

Abstract:

:Alkylpurine-DNA-N-glycosylase (APNG) null mice have been generated by homologous recombination in embryonic stem cells. The null status of the animals was confirmed at the mRNA level by reverse transcription-PCR and by the inability of cell extracts of tissues from the knockout (ko) animals to release 3-methyladenine (3-meA) or 7-methylguanine (7-meG) from 3H-methylated calf thymus DNA in vitro. Following treatment with DNA-methylating agents, increased persistence of 7-meG was found in liver sections of APNG ko mice in comparison with wild-type (wt) mice, demonstrating an in vivo phenotype for the APNG null animals. Unlike other null mutants of the base excision repair pathway, the APNG ko mice exhibit a very mild phenotype, show no outward abnormalities, are fertile, and have an apparently normal life span. Neither a difference in the number of leukocytes in peripheral blood nor a difference in the number of bone marrow polychromatic erythrocytes was found when ko and wt mice were exposed to methylating or chloroethylating agents. These agents also showed similar growth-inhibitory effects in primary embryonic fibroblasts isolated from ko and wt mice. However, treatment with methyl methanesulfonate resulted in three- to fourfold more hprt mutations in splenic T lymphocytes from APNG ko mice than in those from wt mice. These mutations were predominantly single-base-pair changes; in the ko mice, they consisted primarily of AT-->TA and GC-->TA transversions, which most likely are caused by 3-meA and 3- or 7-meG, respectively. These results clearly show an important role for APNG in attenuating the mutagenic effects of N-alkylpurines in vivo.

journal_name

Mol Cell Biol

authors

Elder RH,Jansen JG,Weeks RJ,Willington MA,Deans B,Watson AJ,Mynett KJ,Bailey JA,Cooper DP,Rafferty JA,Heeran MC,Wijnhoven SW,van Zeeland AA,Margison GP

doi

10.1128/mcb.18.10.5828

subject

Has Abstract

pub_date

1998-10-01 00:00:00

pages

5828-37

issue

10

eissn

0270-7306

issn

1098-5549

journal_volume

18

pub_type

杂志文章
  • The oncoprotein kinase chaperone CDC37 functions as an oncogene in mice and collaborates with both c-myc and cyclin D1 in transformation of multiple tissues.

    abstract::CDC37 encodes a 50-kDa protein that targets intrinsically unstable oncoprotein kinases including Cdk4, Raf-1, and v-src to the molecular chaperone Hsp90, an interaction that is thought to be important for the establishment of signaling pathways. CDC37 is required for proliferation in budding yeast and is coexpressed w...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.12.4462-4473.2000

    authors: Stepanova L,Finegold M,DeMayo F,Schmidt EV,Harper JW

    更新日期:2000-06-01 00:00:00

  • Phosphorylation of the RNA polymerase II largest subunit during Xenopus laevis oocyte maturation.

    abstract::Xenopus laevis oogenesis is characterized by an active transcription which ceases abruptly upon maturation. To survey changes in the characteristics of the transcriptional machinery which might contribute to this transcriptional arrest, the phosphorylation status of the RNA polymerase II largest subunit (RPB1 subunit)...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.3.1434

    authors: Bellier S,Dubois MF,Nishida E,Almouzni G,Bensaude O

    更新日期:1997-03-01 00:00:00

  • Replication of DNA minicircles in kinetoplasts isolated from Crithidia fasciculata: structure of nascent minicircles.

    abstract::We have previously described an isolated kinetoplast system from Crithidia fasciculata capable of ATP-dependent replication of kinetoplast DNA minicircles (L. Birkenmeyer and D.S. Ray, J. Biol. Chem. 261: 2362-2368, 1986). We present here the identification of two new minicircle species observed in short pulse-labelin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.1.169

    authors: Sheline C,Melendy T,Ray DS

    更新日期:1989-01-01 00:00:00

  • Roles of fetal G gamma-globin promoter elements and the adult beta-globin 3' enhancer in the stage-specific expression of globin genes.

    abstract::The human fetal G gamma-globin and adult beta-globin genes are expressed in a tissue- and developmental stage-specific pattern in transgenic mice: the G gamma gene in embryonic cells and the beta gene in fetal and adult erythroid cells. Several of the cis-acting DNA sequences thought to be responsible for these patter...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.3.1116

    authors: Perez-Stable C,Costantini F

    更新日期:1990-03-01 00:00:00

  • Analysis of a mutant histone H3 that perturbs the association of Swi/Snf with chromatin.

    abstract::We have isolated new histone H3 mutants in Saccharomyces cerevisiae that confer phenotypes indicative of transcriptional defects. Here we describe the characterization of one such mutant, encoded by the hht2-11 allele, which contains the single amino acid change L61W in the globular domain of H3. Whole-genome expressi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.2.561-572.2004

    authors: Duina AA,Winston F

    更新日期:2004-01-01 00:00:00

  • Nup214 is required for CRM1-dependent nuclear protein export in vivo.

    abstract::Nucleoporins mediate transport of macromolecules across the nuclear pore complex, yet the function of many individual nucleoporins is largely unresolved. To address this question, we depleted cells of the cytoplasmic nucleoporins Nup214/CAN and Nup358/RanBP2 by RNA interference. Depletion of Nup214 resulted in codeple...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00342-06

    authors: Hutten S,Kehlenbach RH

    更新日期:2006-09-01 00:00:00

  • Efficient expression of the Saccharomyces cerevisiae PGK gene depends on an upstream activation sequence but does not require TATA sequences.

    abstract::The Saccharomyces cerevisiae PGK (phosphoglycerate kinase) gene encodes one of the most abundant mRNA and protein species in the cell. To identify the promoter sequences required for the efficient expression of PGK, we undertook a detailed internal deletion analysis of the 5' noncoding region of the gene. Our analysis...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.12.4335

    authors: Ogden JE,Stanway C,Kim S,Mellor J,Kingsman AJ,Kingsman SM

    更新日期:1986-12-01 00:00:00

  • Gene targeting with retroviral vectors: recombination by gene conversion into regions of nonhomology.

    abstract::We have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. St...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.4.1621

    authors: Ellis J,Bernstein A

    更新日期:1989-04-01 00:00:00

  • Mitogenic signaling by colony-stimulating factor 1 and ras is suppressed by the ets-2 DNA-binding domain and restored by myc overexpression.

    abstract::The activity of p21ras is required for the proliferative response to colony-stimulating factor 1 (CSF-1), and signals transduced by both the CSF-1 receptor (CSF-1R) and p21ras stimulate transcription from promoter elements containing overlapping binding sites for Fos/Jun- and Ets-related proteins. A sequence encoding ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.12.5355

    authors: Langer SJ,Bortner DM,Roussel MF,Sherr CJ,Ostrowski MC

    更新日期:1992-12-01 00:00:00

  • c-Myc is necessary for DNA damage-induced apoptosis in the G(2) phase of the cell cycle.

    abstract::The c-myc proto-oncogene encodes a transcription factor that participates in the regulation of cellular proliferation, differentiation, and apoptosis. Ectopic overexpression of c-Myc has been shown to sensitize cells to apoptosis. We report here that cells lacking c-Myc activity due to disruption of the c-myc gene by ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.15.4929-4937.2001

    authors: Adachi S,Obaya AJ,Han Z,Ramos-Desimone N,Wyche JH,Sedivy JM

    更新日期:2001-08-01 00:00:00

  • Domain-specific response of imprinted genes to reduced DNMT1.

    abstract::Imprinted genes are expressed in a monoallelic, parent-of-origin-specific manner. Clusters of imprinted genes are regulated by imprinting control regions (ICRs) characterized by DNA methylation of one allele. This methylation is critical for imprinting; a reduction in the DNA methyltransferase DNMT1 causes a widesprea...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01278-09

    authors: Weaver JR,Sarkisian G,Krapp C,Mager J,Mann MR,Bartolomei MS

    更新日期:2010-08-01 00:00:00

  • The two beta-tubulin genes of Chlamydomonas reinhardtii code for identical proteins.

    abstract::The two beta-tubulin genes of the unicellular green alga Chlamydomonas reinhardtii are expressed coordinately after deflagellation and produce two transcripts of 2.1 and 2.0 kilobases. Full-length cDNA clones corresponding to the transcript of each gene were isolated. DNA sequences were obtained from the cDNA clones a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.12.2686

    authors: Youngblom J,Schloss JA,Silflow CD

    更新日期:1984-12-01 00:00:00

  • Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells.

    abstract::Heparin is required for the binding of basic fibroblast growth factor (bFGF) to high-affinity receptors on cells deficient in cell surface heparan sulfate proteoglycan. So that this heparin requirement could be evaluated in the absence of other cell surface molecules, we designed a simple assay based on a genetically ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.1.240

    authors: Ornitz DM,Yayon A,Flanagan JG,Svahn CM,Levi E,Leder P

    更新日期:1992-01-01 00:00:00

  • The immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription.

    abstract::We demonstrate that the immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription. The enhancer itself, when placed 5' to the bacterial cat or neo genes, is able to direct transcription by using heterogeneous start sites that are generally the same as those found with bona fide I mu ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.2619

    authors: Su LK,Kadesch T

    更新日期:1990-06-01 00:00:00

  • Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14(ARF) tumor suppressor.

    abstract::Normal cells do not divide indefinitely due to a process known as replicative senescence. Human cells arrest growth with a senescent phenotype when they acquire one or more critically short telomeres as a consequence of cell division. Recent evidence suggests that certain types of DNA damage, chromatin remodeling, and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.1.273-285.2000

    authors: Dimri GP,Itahana K,Acosta M,Campisi J

    更新日期:2000-01-01 00:00:00

  • The gene encoding the transcription factor SCIP has features of an expressed retroposon.

    abstract::SCIP is a POU domain transcription factor expressed by glial progenitor cells in the peripheral and central nervous systems (dividing Schwann cells and O-2A cells, respectively), where it appears to act as a repressor of myelin-specific genes. We have isolated genomic clones encoding the rat SCIP gene. Comparison of t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.9.4642

    authors: Kuhn R,Monuki ES,Lemke G

    更新日期:1991-09-01 00:00:00

  • Roles for non-TATA core promoter sequences in transcription and factor binding.

    abstract::Sequence blocks within the core region were swapped among RNA polymerase II promoters to explore effects on transcription in vitro. The pair of blocks flanking TATA strongly influenced general transcription, with an additional effect on promoter activation. These flanking elements induced a change in the ratio of acti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.10.3608-3615.2000

    authors: Wolner BS,Gralla JD

    更新日期:2000-05-01 00:00:00

  • Residues in the Swi5 zinc finger protein that mediate cooperative DNA binding with the Pho2 homeodomain protein.

    abstract::The Swi5 zinc finger and the Pho2 homeodomain DNA-binding proteins bind cooperatively to the HO promoter. Pho2 (also known as Bas2 or Grf10) activates transcription of diverse genes, acting with multiple distinct DNA-binding proteins. We have performed a genetic screen to identify amino acid residues in Swi5 that are ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.11.6436

    authors: Bhoite LT,Stillman DJ

    更新日期:1998-11-01 00:00:00

  • The F-Box DNA helicase Fbh1 prevents Rhp51-dependent recombination without mediator proteins.

    abstract::A key step in homologous recombination is the loading of Rad51 onto single-stranded DNA to form a nucleoprotein filament that promotes homologous DNA pairing and strand exchange. Mediator proteins, such as Rad52 and Rad55-Rad57, are thought to aid filament assembly by overcoming an inhibitory effect of the single-stra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.18.8084-8096.2005

    authors: Osman F,Dixon J,Barr AR,Whitby MC

    更新日期:2005-09-01 00:00:00

  • Peroxisome proliferator-activated receptor alpha regulates a microRNA-mediated signaling cascade responsible for hepatocellular proliferation.

    abstract::Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) leads to hepatocellular proliferation and liver carcinomas. The early events mediating these effects are unknown. A novel mechanism by which PPARalpha regulates gene expression and hepatocellular proliferation was uncovered. MicroRNA (miRNA) ex...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00317-07

    authors: Shah YM,Morimura K,Yang Q,Tanabe T,Takagi M,Gonzalez FJ

    更新日期:2007-06-01 00:00:00

  • PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function.

    abstract::Insults to cellular health cause p53 protein accumulation, and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01475-14

    authors: Keskin N,Deniz E,Eryilmaz J,Un M,Batur T,Ersahin T,Cetin Atalay R,Sakaguchi S,Ellmeier W,Erman B

    更新日期:2015-05-01 00:00:00

  • ATR1, a Saccharomyces cerevisiae gene encoding a transmembrane protein required for aminotriazole resistance.

    abstract::In Saccharomyces cerevisiae, 3-amino-1,2,4-triazole (aminotriazole) competitively inhibits the activity of imidazoleglycerolphosphate dehydratase, the product of the HIS3 gene. Wild-type strains are able to grow in the presence of 10 mM aminotriazole because they induce the level of imidazoleglycerolphosphate dehydrat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.2.664

    authors: Kanazawa S,Driscoll M,Struhl K

    更新日期:1988-02-01 00:00:00

  • Rad53 checkpoint kinase phosphorylation site preference identified in the Swi6 protein of Saccharomyces cerevisiae.

    abstract::Rad53 of Saccharomyces cerevisiae is a checkpoint kinase whose structure and function are conserved among eukaryotes. When a cell detects damaged DNA, Rad53 activity is dramatically increased, which ultimately leads to changes in DNA replication, repair, and cell division. Despite its central role in checkpoint signal...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.10.3405-3416.2003

    authors: Sidorova JM,Breeden LL

    更新日期:2003-05-01 00:00:00

  • TAZ suppresses NFAT5 activity through tyrosine phosphorylation.

    abstract::Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney, and a deficiency of this protein results in multiple rena...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00392-12

    authors: Jang EJ,Jeong H,Han KH,Kwon HM,Hong JH,Hwang ES

    更新日期:2012-12-01 00:00:00

  • Characterization of mice deficient in the Src family nonreceptor tyrosine kinase Frk/rak.

    abstract::Frk/rak belongs to a novel family of Src kinases with epithelial tissue-specific expression. Although developmental expression patterns and functional overexpression in vitro have associated these kinases with growth suppression and differentiation, their physiological functions remain largely unknown. We therefore ge...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.14.5235-5247.2002

    authors: Chandrasekharan S,Qiu TH,Alkharouf N,Brantley K,Mitchell JB,Liu ET

    更新日期:2002-07-01 00:00:00

  • NAD+-dependent deacetylase Hst1p controls biosynthesis and cellular NAD+ levels in Saccharomyces cerevisiae.

    abstract::Nicotine adenine dinucleotide (NAD(+)) performs key roles in electron transport reactions, as a substrate for poly(ADP-ribose) polymerase and NAD(+)-dependent protein deacetylases. In the latter two processes, NAD(+) is consumed and converted to ADP-ribose and nicotinamide. NAD(+) levels can be maintained by regenerat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.19.7044-7054.2003

    authors: Bedalov A,Hirao M,Posakony J,Nelson M,Simon JA

    更新日期:2003-10-01 00:00:00

  • Human heat shock factors 1 and 2 are differentially activated and can synergistically induce hsp70 gene transcription.

    abstract::Two members of the heat shock transcription factor (HSF) family, HSF1 and HSF2, both function as transcriptional activators of heat shock gene expression. However, the inducible DNA-binding activities of these two factors are regulated by distinct pathways. HSF1 is activated by heat shock and other forms of stress, wh...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.3.2087

    authors: Sistonen L,Sarge KD,Morimoto RI

    更新日期:1994-03-01 00:00:00

  • Impaired binding of 14-3-3 to C-RAF in Noonan syndrome suggests new approaches in diseases with increased Ras signaling.

    abstract::The Ras-RAF-mitogen-activated protein kinase (Ras-RAF-MAPK) pathway is overactive in many cancers and in some developmental disorders. In one of those disorders, namely, Noonan syndrome, nine activating C-RAF mutations cluster around Ser(259), a regulatory site for inhibition by 14-3-3 proteins. We show that these mut...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01636-09

    authors: Molzan M,Schumacher B,Ottmann C,Baljuls A,Polzien L,Weyand M,Thiel P,Rose R,Rose M,Kuhenne P,Kaiser M,Rapp UR,Kuhlmann J,Ottmann C

    更新日期:2010-10-01 00:00:00

  • Transcriptional and posttranscriptional regulation of the proliferating cell nuclear antigen gene.

    abstract::The steady-state mRNA levels of the proliferating cell nuclear antigen (PCNA) gene are growth regulated. In a previous paper (L. Ottavio, C.-D. Chang, M. G. Rizzo, S. Travali, C. Casadevall, and R. Baserga, Mol. Cell. Biol. 10:303-309, 1990), we reported that introns (especially intron 4) participate in growth regulat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.7.3289

    authors: Chang CD,Ottavio L,Travali S,Lipson KE,Baserga R

    更新日期:1990-07-01 00:00:00

  • Interaction between the yeast mitochondrial and nuclear genomes influences the abundance of novel transcripts derived from the spacer region of the nuclear ribosomal DNA repeat.

    abstract::We have identified stable transcripts from the so-called nontranscribed spacer region (NTS) of the nuclear ribosomal DNA repeat in certain respiration-deficient strains of Saccharomyces cerevisiae. These RNAs, which are transcribed from the same strand as is the 37S rRNA precursor, are 500 to 800 nucleotides long and ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.5.1897

    authors: Parikh VS,Conrad-Webb H,Docherty R,Butow RA

    更新日期:1989-05-01 00:00:00