A Ku80 fragment with dominant negative activity imparts a radiosensitive phenotype to CHO-K1 cells.

Abstract:

:DNA non-homologous end joining, the major mechanism for the repair of DNA double-strands breaks (DSB) in mammalian cells requires the DNA-dependent protein kinase (DNA-PK), a complex composed of a large catalytic subunit of 460 kDa (DNA-PKcs) and the heterodimer Ku70-Ku80 that binds to double-stranded DNA ends. Mutations in any of the three subunits of DNA-PK lead to extreme radiosensitivity and DSB repair deficiency. Here we show that the 283 C-terminal amino acids of Ku80 introduced into the Chinese hamster ovary cell line CHO-K1 have a dominant negative effect. Expression of Ku(449-732) in CHO cells was verified by northern blot analysis and resulted in decreased Ku-dependent DNA end-binding activity, a diminished capacity to repair DSBs as determined by pulsed field gel electrophoresis and decreased radioresistance determined by clonogenic survival. The stable modifications observed at the molecular and cellular level suggest that this fragment of Ku80 confers a dominant negative effect providing an important mechanism to sensitise radioresistant cells.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Marangoni E,Foray N,O'Driscoll M,Douc-Rasy S,Bernier J,Bourhis J,Jeggo P

doi

10.1093/nar/28.23.4778

keywords:

subject

Has Abstract

pub_date

2000-12-01 00:00:00

pages

4778-82

issue

23

eissn

0305-1048

issn

1362-4962

journal_volume

28

pub_type

杂志文章
  • Structural characterization of a ribonuclease III processing signal.

    abstract::The structure of a ribonuclease III processing signal from bacteriophage T7 was examined by NMR spectroscopy, optical melting, and chemical and enzymatic modification. A 41 nucleotide variant of the T7 R1.1 processing signal has two Watson-Crick base-paired helices separated by an internal loop, consistent with its pr...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/22.4.604

    authors: Schweisguth DC,Chelladurai BS,Nicholson AW,Moore PB

    更新日期:1994-02-25 00:00:00

  • Dynamic structural insights into the molecular mechanism of DNA unwinding by the bacteriophage T7 helicase.

    abstract::The hexametric T7 helicase (gp4) adopts a spiral lock-washer form and encircles a coil-like DNA (tracking) strand with two nucleotides bound to each subunit. However, the chemo-mechanical coupling mechanism in unwinding has yet to be elucidated. Here, we utilized nanotensioner-enhanced Förster resonance energy transfe...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa057

    authors: Ma JB,Chen Z,Xu CH,Huang XY,Jia Q,Zou ZY,Mi CY,Ma DF,Lu Y,Zhang HD,Li M

    更新日期:2020-04-06 00:00:00

  • New substituted quinoxalines inhibit triple-negative breast cancer by specifically downregulating the c-MYC transcription.

    abstract::Conventional chemotherapy remains the primary treatment option for triple-negative breast cancer (TNBC). However, the current chemotherapeutic drugs have limited effects on TNBC, and often lead to serious side effects as well as drug resistance. Thus, more effective therapeutic options are sorely needed. As c-MYC onco...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz835

    authors: Hu MH,Wu TY,Huang Q,Jin G

    更新日期:2019-11-18 00:00:00

  • 3D-Image analysis platform monitoring relocation of pluripotency genes during reprogramming.

    abstract::Nuclear organization of chromatin is an important level of genome regulation with positional changes of genes occurring during reprogramming. Inherent variability of biological specimens, wide variety of sample preparation and imaging conditions, though pose significant challenges to data analysis and comparison. Here...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr486

    authors: Jost KL,Haase S,Smeets D,Schrode N,Schmiedel JM,Bertulat B,Herzel H,Cremer M,Cardoso MC

    更新日期:2011-09-01 00:00:00

  • Identification of active miRNA promoters from nuclear run-on RNA sequencing.

    abstract::The genome-wide identification of microRNA transcription start sites (miRNA TSSs) is essential for understanding how miRNAs are regulated in development and disease. In this study, we developed mirSTP (mirna transcription Start sites Tracking Program), a probabilistic model for identifying active miRNA TSSs from nasce...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkx318

    authors: Liu Q,Wang J,Zhao Y,Li CI,Stengel KR,Acharya P,Johnston G,Hiebert SW,Shyr Y

    更新日期:2017-07-27 00:00:00

  • Length mutations in human mitochondrial DNA: direct sequencing of enzymatically amplified DNA.

    abstract::A specific segment of mitochondrial DNA from 18 people was examined by two methods of direct DNA sequencing. This segment includes a small noncoding region (V) shown before by restriction analysis to exhibit length polymorphism. All 11 of the human mtDNAs previously reported to have a deletion in this region proved to...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/15.2.529

    authors: Wrischnik LA,Higuchi RG,Stoneking M,Erlich HA,Arnheim N,Wilson AC

    更新日期:1987-01-26 00:00:00

  • Different binding site requirements for binding and activation for the bipartite enhancer factor EF-1A.

    abstract::The human transcription factor EF-1A binds to the purine-rich E1A core enhancer sequence in the adenovirus E1A and E4 and polyomavirus enhancer regions. The consensus binding site for EF-1A resembles that of members of the ets domain protein family. EF-1A activation of transcription requires a dimeric binding site. An...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/20.24.6555

    authors: Bolwig GM,Bruder JT,Hearing P

    更新日期:1992-12-25 00:00:00

  • Interaction of p53 with the human Rad51 protein.

    abstract::p53 is thought to function in the maintenance of genomic stability by modulating transcription and interacting with cellular proteins to influence the cell cycle, DNA repair and apoptosis. p53 mutations occur in >50% of human cancers, and cells which lack wild type p53 accumulate karyotypic abnormalities such as ampli...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.19.3868

    authors: Buchhop S,Gibson MK,Wang XW,Wagner P,Stürzbecher HW,Harris CC

    更新日期:1997-10-01 00:00:00

  • Plasmodium falciparum heterochromatin protein 1 binds to tri-methylated histone 3 lysine 9 and is linked to mutually exclusive expression of var genes.

    abstract::Increasing experimental evidence shows a prominent role of histone modifications in the coordinated control of gene expression in the human malaria parasite Plasmodium falciparum. The search for the histone-mark-reading machinery that translates histone modifications into biological processes, such as formation of het...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkp115

    authors: Pérez-Toledo K,Rojas-Meza AP,Mancio-Silva L,Hernández-Cuevas NA,Delgadillo DM,Vargas M,Martínez-Calvillo S,Scherf A,Hernandez-Rivas R

    更新日期:2009-05-01 00:00:00

  • Transcription factor binding and spacing constraints in the human beta-actin proximal promoter.

    abstract::The human beta-actin promoter, including its 5' flanking region and 5' untranslated region, is ubiquitously active in mammalian cells in culture. In this report we investigated the transcriptional activity of, and the protein-DNA interactions that occur within, the proximal region of the human beta-actin promoter. Eff...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/19.24.6913

    authors: Danilition SL,Frederickson RM,Taylor CY,Miyamoto NG

    更新日期:1991-12-25 00:00:00

  • Oligonucleotide mutagenesis of the lacPUV5 promoter.

    abstract::Synthetic oligonucleotides were used to introduce mutations into the lacPUV5 promoter. Four mutations were obtained at positions -13, -14, and -15, with respect to the transcriptional start site. The effects of these mutations were measured in vivo and the results are discussed with respect to the consensus sequence a...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/12.9.4011

    authors: Munson LM,Mandecki W,Caruthers MH,Reznikoff WS

    更新日期:1984-05-11 00:00:00

  • Strong dependence between functional domains in a dual-function snoRNA infers coupling of rRNA processing and modification events.

    abstract::Most small nucleolar RNAs (snoRNAs) guide rRNA nucleotide modifications, some participate in pre-rRNA cleavages, and a few have both functions. These activities involve direct base-pairing of the snoRNA with pre-rRNA using different domains. It is not known if the modification and processing functions occur independen...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkq043

    authors: Liang XH,Liu Q,Liu Q,King TH,Fournier MJ

    更新日期:2010-06-01 00:00:00

  • Gene expression atlas at the European bioinformatics institute.

    abstract::The Gene Expression Atlas (http://www.ebi.ac.uk/gxa) is an added-value database providing information about gene expression in different cell types, organism parts, developmental stages, disease states, sample treatments and other biological/experimental conditions. The content of this database derives from curation, ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkp936

    authors: Kapushesky M,Emam I,Holloway E,Kurnosov P,Zorin A,Malone J,Rustici G,Williams E,Parkinson H,Brazma A

    更新日期:2010-01-01 00:00:00

  • Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.

    abstract::A common goal in the discovery of rare functional DNA variants via medical resequencing is to incur a relatively lower proportion of false positive base-calls. We developed a novel statistical method for resequencing arrays (SRMA, sequence robust multi-array analysis) to increase the accuracy of detecting rare variant...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkq750

    authors: Wang W,Shen P,Thiyagarajan S,Lin S,Palm C,Horvath R,Klopstock T,Cutler D,Pique L,Schrijver I,Davis RW,Mindrinos M,Speed TP,Scharfe C

    更新日期:2011-01-01 00:00:00

  • Ser-tRNAs from bovine mitochondrion form ternary complexes with bacterial elongation factor Tu and GTP.

    abstract::Transfer ribonucleic acids were isolated from mitochondria of bovine heart and aminoacylated in vitro by a crude mitochondrial enzyme. Ser-tRNASerUCN and Ser-tRNASerAGY were isolated and characterized by partial sequencing. Although these tRNAs possess unique structural features not found in any bacterial tRNA, they f...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/14.18.7175

    authors: Gebhardt-Singh E,Sprinzl M

    更新日期:1986-09-25 00:00:00

  • Human Rad51 protein displays enhanced homologous pairing of DNA sequences resembling those at genetically unstable loci.

    abstract::DNA strand exchange, the central step of homologous recombination, is considered to occur approximately independently of DNA sequence content. However, certain prokaryotic and eukaryotic genomic loci display either an enhanced or reduced frequency of genetic exchange. Here we show that the Homo sapiens DNA strand exch...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkl355

    authors: Seitz EM,Kowalczykowski SC

    更新日期:2006-05-24 00:00:00

  • Unusual structural features of the 5S ribosomal RNA from Streptococcus cremoris.

    abstract::The nucleotide sequence of the 5S ribosomal RNA of Streptococcus cremoris has been determined. The sequence is 5' (sequence in text) 3'. Comparison of the S. cremoris 5S RNA sequence to an updated prokaryotic generalized 5S RNA structural model shows that this 5S RNA contains some unusual structural features. These fe...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/11.21.7569

    authors: Neimark H,Andersen J,Delihas N

    更新日期:1983-11-11 00:00:00

  • ChIP-Enrich: gene set enrichment testing for ChIP-seq data.

    abstract::Gene set enrichment testing can enhance the biological interpretation of ChIP-seq data. Here, we develop a method, ChIP-Enrich, for this analysis which empirically adjusts for gene locus length (the length of the gene body and its surrounding non-coding sequence). Adjustment for gene locus length is necessary because ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gku463

    authors: Welch RP,Lee C,Imbriano PM,Patil S,Weymouth TE,Smith RA,Scott LJ,Sartor MA

    更新日期:2014-07-01 00:00:00

  • Incorporation of 2'-amido-nucleosides in oligodeoxynucleotides and oligoribonucleotides as a model for 2'-linked conjugates.

    abstract::The functionalisation of oligodeoxynucleotides and oligoribonucleotides by incorporation of 2'-amido-2'-deoxyribonucleosides, possibly containing a reporter group via the 2'-amido bond, was examined. Therefore 2'-acetamido-ribonucleosides containing a small methyl group at the 2'-amido bond were synthesized as model c...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/23.1.51

    authors: Hendrix C,Devreese B,Rozenski J,van Aerschot A,De Bruyn A,Van Beeumen J,Herdewijn P

    更新日期:1995-01-11 00:00:00

  • Association of antisense oligonucleotides with lipoproteins prolongs the plasma half-life and modifies the tissue distribution.

    abstract::In order to direct antisense oligonucleotides to specific tissues or cell types in vivo, we are exploring the possibility to utilize lipoproteins as transport vehicles. A 16-mer oligonucleotide (ODN) was derivatized at the 5' prime through a 32P phosphate spacer with cholesterol, yielding a 32P-labeled amphiphatic cho...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/19.17.4695

    authors: de Smidt PC,Le Doan T,de Falco S,van Berkel TJ

    更新日期:1991-09-11 00:00:00

  • Role of LrpC from Bacillus subtilis in DNA transactions during DNA repair and recombination.

    abstract::Bacillus subtilis LrpC is a sequence-independent DNA-binding and DNA-bending protein, which binds both single-stranded (ss) and double-stranded (ds) DNA and facilitates the formation of higher order protein-DNA complexes in vitro. LrpC binds at different sites within the same DNA molecule promoting intramolecular liga...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkj418

    authors: López-Torrejón G,Martínez-Jiménez MI,Ayora S

    更新日期:2006-01-10 00:00:00

  • Detecting tissue-specific regulation of alternative splicing as a qualitative change in microarray data.

    abstract::Alternative splicing has recently emerged as a major mechanism of regulation in the human genome, occurring in perhaps 40-60% of human genes. Thus, microarray studies of functional regulation could, in principle, be extended to detect not only the changes in the overall expression of a gene, but also changes in its sp...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gnh173

    authors: Le K,Mitsouras K,Roy M,Wang Q,Xu Q,Nelson SF,Lee C

    更新日期:2004-12-14 00:00:00

  • Structures of m-iodo Hoechst-DNA complexes in crystals with reduced solvent content: implications for minor groove binder drug design.

    abstract::The DNA photosensitisers m-iodo Hoechst and m-iodo, p-methoxy Hoechst have been co-crystallised with the oligonucleotide d(CGCGAATTCGCG)(2)and their crystal structures determined. The crystals were then subjected to slow dehydration, which reduced their solvent contents from 40 (normal) to 30 (partially dehydrated) an...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/28.5.1252

    authors: Squire CJ,Baker LJ,Clark GR,Martin RF,White J

    更新日期:2000-03-01 00:00:00

  • RegAnalyst: a web interface for the analysis of regulatory motifs, networks and pathways.

    abstract::RegAnalyst is a user-friendly web interface that integrates MoPP (Motif Prediction Program), MyPatternFinder (pattern detection tool) and MycoRegDB (mycobacterial promoter and regulatory elements database). Since motif discovery is a challenging task, numerous tools have been developed over the past few years. Strikin...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkp388

    authors: Sharma D,Mohanty D,Surolia A

    更新日期:2009-07-01 00:00:00

  • VAMPIRE microarray suite: a web-based platform for the interpretation of gene expression data.

    abstract::Microarrays are invaluable high-throughput tools used to snapshot the gene expression profiles of cells and tissues. Among the most basic and fundamental questions asked of microarray data is whether individual genes are significantly activated or repressed by a particular stimulus. We have previously presented two Ba...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gki443

    authors: Hsiao A,Ideker T,Olefsky JM,Subramaniam S

    更新日期:2005-07-01 00:00:00

  • Pscan: finding over-represented transcription factor binding site motifs in sequences from co-regulated or co-expressed genes.

    abstract::The first step in gene expression, transcription, is modulated by the interaction of transcription factors with their corresponding binding sites on the DNA sequence. Pscan is a software tool that scans a set of sequences (e.g. promoters) from co-regulated or co-expressed genes with motifs describing the binding speci...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkp464

    authors: Zambelli F,Pesole G,Pavesi G

    更新日期:2009-07-01 00:00:00

  • The UNITE database for molecular identification of fungi: handling dark taxa and parallel taxonomic classifications.

    abstract::UNITE (https://unite.ut.ee/) is a web-based database and sequence management environment for the molecular identification of fungi. It targets the formal fungal barcode-the nuclear ribosomal internal transcribed spacer (ITS) region-and offers all ∼1 000 000 public fungal ITS sequences for reference. These are clustere...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gky1022

    authors: Nilsson RH,Larsson KH,Taylor AFS,Bengtsson-Palme J,Jeppesen TS,Schigel D,Kennedy P,Picard K,Glöckner FO,Tedersoo L,Saar I,Kõljalg U,Abarenkov K

    更新日期:2019-01-08 00:00:00

  • An hnRNP-like RNA-binding protein affects alternative splicing by in vivo interaction with transcripts in Arabidopsis thaliana.

    abstract::Alternative splicing (AS) of pre-mRNAs is an important regulatory mechanism shaping the transcriptome. In plants, only few RNA-binding proteins are known to affect AS. Here, we show that the glycine-rich RNA-binding protein AtGRP7 influences AS in Arabidopsis thaliana. Using a high-resolution RT-PCR-based AS panel, we...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks873

    authors: Streitner C,Köster T,Simpson CG,Shaw P,Danisman S,Brown JW,Staiger D

    更新日期:2012-12-01 00:00:00

  • Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications.

    abstract::Recent advances in DNA-sequencing technology have made it possible to obtain large datasets of small RNA sequences. Here we demonstrate that not all non-perfectly matched small RNA sequences are simple technological sequencing errors, but many hold valuable biological information. Analysis of three small RNA datasets ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章,meta分析

    doi:10.1093/nar/gkp093

    authors: Ebhardt HA,Tsang HH,Dai DC,Liu Y,Bostan B,Fahlman RP

    更新日期:2009-05-01 00:00:00

  • Quantitation of DNase I sensitivity in Xenopus chromatin containing active and inactive globin, albumin and vitellogenin genes.

    abstract::The disappearance of defined restriction fragments of the beta 1-globin, an albumin and the A1 vitellogenin gene was quantitated after DNase I digestion and expressed by a sensitivity factor defined by a mathematical model. Analysis of naked DNA showed that the gene fragments have similar but not identical sensitivity...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/9.11.2455

    authors: Felber BK,Gerber-Huber S,Meier C,May FE,Westley B,Weber R,Ryffel GU

    更新日期:1981-06-11 00:00:00