Metnase promotes restart and repair of stalled and collapsed replication forks.

Abstract:

:Metnase is a human protein with methylase (SET) and nuclease domains that is widely expressed, especially in proliferating tissues. Metnase promotes non-homologous end-joining (NHEJ), and knockdown causes mild hypersensitivity to ionizing radiation. Metnase also promotes plasmid and viral DNA integration, and topoisomerase IIα (TopoIIα)-dependent chromosome decatenation. NHEJ factors have been implicated in the replication stress response, and TopoIIα has been proposed to relax positive supercoils in front of replication forks. Here we show that Metnase promotes cell proliferation, but it does not alter cell cycle distributions, or replication fork progression. However, Metnase knockdown sensitizes cells to replication stress and confers a marked defect in restart of stalled replication forks. Metnase promotes resolution of phosphorylated histone H2AX, a marker of DNA double-strand breaks at collapsed forks, and it co-immunoprecipitates with PCNA and RAD9, a member of the PCNA-like RAD9-HUS1-RAD1 intra-S checkpoint complex. Metnase also promotes TopoIIα-mediated relaxation of positively supercoiled DNA. Metnase is not required for RAD51 focus formation after replication stress, but Metnase knockdown cells show increased RAD51 foci in the presence or absence of replication stress. These results establish Metnase as a key factor that promotes restart of stalled replication forks, and implicate Metnase in the repair of collapsed forks.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

De Haro LP,Wray J,Williamson EA,Durant ST,Corwin L,Gentry AC,Osheroff N,Lee SH,Hromas R,Nickoloff JA

doi

10.1093/nar/gkq339

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

5681-91

issue

17

eissn

0305-1048

issn

1362-4962

pii

gkq339

journal_volume

38

pub_type

杂志文章
  • Distinct functions of the RNA polymerase σ subunit region 3.2 in RNA priming and promoter escape.

    abstract::The σ subunit of bacterial RNA polymerase (RNAP) has been implicated in all steps of transcription initiation, including promoter recognition and opening, priming of RNA synthesis, abortive initiation and promoter escape. The post-promoter-recognition σ functions were proposed to depend on its conserved region σ3.2 th...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt1384

    authors: Pupov D,Kuzin I,Bass I,Kulbachinskiy A

    更新日期:2014-04-01 00:00:00

  • A non-canonical multisubunit RNA polymerase encoded by the AR9 phage recognizes the template strand of its uracil-containing promoters.

    abstract::AR9 is a giant Bacillus subtilis phage whose uracil-containing double-stranded DNA genome encodes distant homologs of β and β' subunits of bacterial RNA polymerase (RNAP). The products of these genes are thought to assemble into two non-canonical multisubunit RNAPs - a virion RNAP (vRNAP) that is injected into the hos...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkx264

    authors: Sokolova M,Borukhov S,Lavysh D,Artamonova T,Khodorkovskii M,Severinov K

    更新日期:2017-06-02 00:00:00

  • Effect of UV-irradiation on DNA replication of the parvovirus minute-virus-of-mice in mouse fibroblasts.

    abstract::The effect of UV-irradiation on the conversion of the single-stranded DNA of the parvovirus Minute-Virus-of-Mice (MVM) to duplex Replicative Forms (RF) was studied after infection of mouse A9 fibroblasts. UV-irradiation of the virus prior to infection of unirradiated cells resulted in a dose-dependent, single-hit, inh...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/10.8.2577

    authors: Rommelaere J,Ward DC

    更新日期:1982-04-24 00:00:00

  • Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae.

    abstract::Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa545

    authors: Prada-Luengo I,Møller HD,Henriksen RA,Gao Q,Larsen CE,Alizadeh S,Maretty L,Houseley J,Regenberg B

    更新日期:2020-08-20 00:00:00

  • Replication stress by Py-Im polyamides induces a non-canonical ATR-dependent checkpoint response.

    abstract::Pyrrole-imidazole polyamides targeted to the androgen response element were cytotoxic in multiple cell lines, independent of intact androgen receptor signaling. Polyamide treatment induced accumulation of S-phase cells and of PCNA replication/repair foci. Activation of a cell cycle checkpoint response was evidenced by...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gku866

    authors: Martínez TF,Phillips JW,Karanja KK,Polaczek P,Wang CM,Li BC,Campbell JL,Dervan PB

    更新日期:2014-10-01 00:00:00

  • Improved detection of small deletions in complex pools of DNA.

    abstract::About 40% of the genes in the nematode Caenorhabditis elegans have homologs in humans. Based on the history of this model system, it is clear that the application of genetic methods to the study of this set of genes would provide important clues to their function in humans. To facilitate such genetic studies, we are e...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gnf051

    authors: Edgley M,D'Souza A,Moulder G,McKay S,Shen B,Gilchrist E,Moerman D,Barstead R

    更新日期:2002-06-15 00:00:00

  • Signatures of accelerated somatic evolution in gene promoters in multiple cancer types.

    abstract::Cancer-associated somatic mutations outside protein-coding regions remain largely unexplored. Analyses of the TERT locus have indicated that non-coding regulatory mutations can be more frequent than previously suspected and play important roles in oncogenesis. Using a computational method called SASE-hunter, developed...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv419

    authors: Smith KS,Yadav VK,Pedersen BS,Shaknovich R,Geraci MW,Pollard KS,De S

    更新日期:2015-06-23 00:00:00

  • DNA sequence analysis: a general, simple and rapid method for sequencing large oligodeoxyribonucleotide fragments by mapping.

    abstract::Several electrophoretic and chromatographic systems have been investigated and compared for sequence analysis of oligodeoxyribonucleotides. Three systems were found to be useful for the separation of a series of sequential degradation products resulting from a labeled oligonucleotide: (I) 2-D electrophoresisdagger; (I...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/1.3.331

    authors: Jay E,Bambara R,Padmanabhan R,Wu R

    更新日期:1974-03-01 00:00:00

  • Investigating the role of the Est3 protein in yeast telomere replication.

    abstract::The Est3 subunit of yeast telomerase, which adopts a predicted OB-fold, is essential for telomere replication. To assess the possible contributions that Est3 might make to enzyme catalysis, we compared telomerase activity from wild type and est3-Delta strains of Saccharomyces castellii, which revealed that loss of the...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkp1173

    authors: Lee J,Mandell EK,Rao T,Wuttke DS,Lundblad V

    更新日期:2010-04-01 00:00:00

  • LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro.

    abstract::Transcriptional co-activator LEDGF/p75 is the major cellular interactor of HIV-1 integrase (IN), critical to efficient viral replication. In this work, a series of INs from the Betaretrovirus, Gammaretrovirus, Deltaretrovirus, Spumavirus and Lentivirus retroviral genera were tested for interaction with the host factor...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkl885

    authors: Cherepanov P

    更新日期:2007-01-01 00:00:00

  • PubChem's BioAssay Database.

    abstract::PubChem (http://pubchem.ncbi.nlm.nih.gov) is a public repository for biological activity data of small molecules and RNAi reagents. The mission of PubChem is to deliver free and easy access to all deposited data, and to provide intuitive data analysis tools. The PubChem BioAssay database currently contains 500,000 des...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr1132

    authors: Wang Y,Xiao J,Suzek TO,Zhang J,Wang J,Zhou Z,Han L,Karapetyan K,Dracheva S,Shoemaker BA,Bolton E,Gindulyte A,Bryant SH

    更新日期:2012-01-01 00:00:00

  • Differences in unwinding of supercoiled DNA induced by the two enantiomers of anti-benzo[a]pyrene diol epoxide.

    abstract::The unwinding of supercoiled phi X174 RFI DNA induced by the tumorigenic (+) and non-tumorigenic (-) enantiomers of trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) has been investigated by agarose slab-gel and ethidium titration tube gel electrophoresis. The differences in adduct conformat...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/20.23.6167

    authors: Xu R,Birke S,Carberry SE,Geacintov NE,Swenberg CE,Harvey RG

    更新日期:1992-12-11 00:00:00

  • CentroidHomfold-LAST: accurate prediction of RNA secondary structure using automatically collected homologous sequences.

    abstract::Although secondary structure predictions of an individual RNA sequence have been widely used in a number of sequence analyses of RNAs, accuracy is still limited. Recently, we proposed a method (called 'CentroidHomfold'), which includes information about homologous sequences into the prediction of the secondary structu...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr290

    authors: Hamada M,Yamada K,Sato K,Frith MC,Asai K

    更新日期:2011-07-01 00:00:00

  • A compact form of double-stranded RNA in solutions containing poly(ethyleneglycol).

    abstract::Molecules of single-stranded ribosomal RNA and double-stranded replicative form of phage f2 RNA (dsRNA) adopt a compact form in solutions, containing sufficiently high concentrations of salt (NaCl) and polymer (PEG). However, only in the cases of native dsRNA molecules the compact particles are characterized by a regu...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/3.6.1533

    authors: Evdokimov YM,Pyatigorskaya TL,Kadikov VA,Polyvtsev OF,Doskocil J,Koudelka J,Varshavsky YM

    更新日期:1976-06-01 00:00:00

  • Interdependence between DNA template secondary structure and priming efficiencies of short primers.

    abstract::Here we analyze the effect of DNA folding on the performance of short primers and describe a simple technique for assessing hitherto uncertain values of thermodynamic parameters that determine the folding of single-stranded DNA into secondary structure. An 8mer with two degenerate positions is extended simultaneously ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/26.23.5525

    authors: Lvovsky L,Ioshikhes I,Raja MC,Zevin-Sonkin D,Sobolev IA,Liberzon A,Shwartzburd J,Ulanovsky LE

    更新日期:1998-12-01 00:00:00

  • SDPMOD: an automated comparative modeling server for small disulfide-bonded proteins.

    abstract::Small disulfide-bonded proteins (SDPs) are rich sources for therapeutic drugs. Designing drugs from these proteins requires three-dimensional structural information, which is only available for a subset of these proteins. SDPMOD addresses this deficit in structural information by providing a freely available automated...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkh394

    authors: Kong L,Lee BT,Tong JC,Tan TW,Ranganathan S

    更新日期:2004-07-01 00:00:00

  • How 'arm-twisting' by the inducer triggers activation of the MalT transcription factor, a typical signal transduction ATPase with numerous domains (STAND).

    abstract::Signal transduction ATPases with numerous domains (STAND) get activated through inducer-dependent assembly into multimeric platforms. This switch relies on the conversion of their nucleotide-binding oligomerization domain (NOD) from a closed, ADP-bound form to an open, ATP-bound form. The NOD closed form is stabilized...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv158

    authors: Danot O

    更新日期:2015-03-31 00:00:00

  • A new G-tailing method for the determination of the poly(A) tail length applied to hepatitis A virus RNA.

    abstract::To study the role of the poly(A) tail length during the replication of poly(A)-containing plus-strand RNA virus, we have developed a simple reverse transcription polymerase chain reaction (RT-PCR)-based method that substantially improves the previously reported PAT [poly(A) test] assay. In contrast to the PAT assay, t...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/29.12.e57

    authors: Kusov YY,Shatirishvili G,Dzagurov G,Gauss-Müller V

    更新日期:2001-06-15 00:00:00

  • LYRA, a webserver for lymphocyte receptor structural modeling.

    abstract::The accurate structural modeling of B- and T-cell receptors is fundamental to gain a detailed insight in the mechanisms underlying immunity and in developing new drugs and therapies. The LYRA (LYmphocyte Receptor Automated modeling) web server (http://www.cbs.dtu.dk/services/LYRA/) implements a complete and automated ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv535

    authors: Klausen MS,Anderson MV,Jespersen MC,Nielsen M,Marcatili P

    更新日期:2015-07-01 00:00:00

  • Nucleotide sequences of 5S ribosomal RNA from four oomycete and chytrid water molds.

    abstract::The nucleotide sequences of the 5S rRNAs of the oomycete water molds Saprolegnia ferax and Pythium hydnosporum and of the chytrid water molds Blastocladiella simplex and Phlyctochytrium irregulare were determined by chemical and enzymatic partial degradation of 3' and 5' end-labelled molecules, followed by gel sequenc...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/10.18.5717

    authors: Walker WF,Doolittle WF

    更新日期:1982-09-25 00:00:00

  • A unique tRNA recognition mechanism of Caenorhabditis elegans mitochondrial EF-Tu2.

    abstract::Nematode mitochondria expresses two types of extremely truncated tRNAs that are specifically recognized by two distinct elongation factor Tu (EF-Tu) species named EF-Tu1 and EF-Tu2. This is unlike the canonical EF-Tu molecule that participates in the standard protein biosynthesis systems, which basically recognizes al...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gki784

    authors: Suematsu T,Sato A,Sakurai M,Watanabe K,Ohtsuki T

    更新日期:2005-08-19 00:00:00

  • Cyber-T web server: differential analysis of high-throughput data.

    abstract::The Bayesian regularization method for high-throughput differential analysis, described in Baldi and Long (A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inferences of gene changes. Bioinformatics 2001: 17: 509-519) and implemented in the Cyber-T web server, is ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks420

    authors: Kayala MA,Baldi P

    更新日期:2012-07-01 00:00:00

  • Targeted resequencing of HIV variants by microarray thermodynamics.

    abstract::Within a single infected individual, a virus population can have a high genomic variability. In the case of HIV, several mutations can be present even in a small genomic window of 20-30 nucleotides. For diagnostics purposes, it is often needed to resequence genomic subsets where crucial mutations are known to occur. I...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt682

    authors: Hadiwikarta WW,Van Dorst B,Hollanders K,Stuyver L,Carlon E,Hooyberghs J

    更新日期:2013-10-01 00:00:00

  • Insertion of the T3 DNA polymerase thioredoxin binding domain enhances the processivity and fidelity of Taq DNA polymerase.

    abstract::Insertion of the T3 DNA polymerase thioredoxin binding domain (TBD) into the distantly related thermostable Taq DNA polymerase at an analogous position in the thumb domain, converts the Taq DNA polymerase from a low processive to a highly processive enzyme. Processivity is dependent on the presence of thioredoxin. The...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkg667

    authors: Davidson JF,Fox R,Harris DD,Lyons-Abbott S,Loeb LA

    更新日期:2003-08-15 00:00:00

  • Detection of triple-helix related structures adopted by poly(dG)-poly(dC) sequences in supercoiled plasmid DNA.

    abstract::Negative superhelical strain induces the poly(dG)-poly(dC) sequence to adopt two totally different types of triple-helices, either a dG.dG.dC triplex in the presence of Mg(+)+ at both neutral and acidic pHs or a protonated dC+.dG.dC triplex in the absence of Mg(+)+ ions at acidic pH (1). To examine whether there are s...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/19.15.4267

    authors: Kohwi-Shigematsu T,Kohwi Y

    更新日期:1991-08-11 00:00:00

  • Coordination logic of the sensing machinery in the transcriptional regulatory network of Escherichia coli.

    abstract::The active and inactive state of transcription factors in growing cells is usually directed by allosteric physicochemical signals or metabolites, which are in turn either produced in the cell or obtained from the environment by the activity of the products of effector genes. To understand the regulatory dynamics and t...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkm743

    authors: Janga SC,Salgado H,Martínez-Antonio A,Collado-Vides J

    更新日期:2007-01-01 00:00:00

  • TRAP150 interacts with the RNA-binding domain of PSF and antagonizes splicing of numerous PSF-target genes in T cells.

    abstract::PSF (a.k.a. SFPQ) is a ubiquitously expressed, essential nuclear protein with important roles in DNA damage repair and RNA biogenesis. In stimulated T cells, PSF binds to and suppresses the inclusion of CD45 exon 4 in the final mRNA; however, in resting cells, TRAP150 binds PSF and prevents access to the CD45 RNA, tho...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv816

    authors: Yarosh CA,Tapescu I,Thompson MG,Qiu J,Mallory MJ,Fu XD,Lynch KW

    更新日期:2015-10-15 00:00:00

  • VLDP web server: a powerful geometric tool for analysing protein structures in their environment.

    abstract::Protein structures are an ensemble of atoms determined experimentally mostly by X-ray crystallography or Nuclear Magnetic Resonance. Studying 3D protein structures is a key point for better understanding protein function at a molecular level. We propose a set of accurate tools, for analysing protein structures, based ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt509

    authors: Esque J,Léonard S,de Brevern AG,Oguey C

    更新日期:2013-07-01 00:00:00

  • Structural insights into NusG regulating transcription elongation.

    abstract::NusG is an essential transcription factor that plays multiple key regulatory roles in transcription elongation, termination and coupling translation and transcription. The core role of NusG is to enhance transcription elongation and RNA polymerase processivity. Here, we present the structure of Escherichia coli RNA po...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkw1159

    authors: Liu B,Steitz TA

    更新日期:2017-01-25 00:00:00

  • Zinc ions are differentially required for the transcription of ribosomal 5S RNA and tRNA in a HeLa-cell extract.

    abstract::Chelation of divalent cations by 5 mM EDTA and subsequent removal by dialysis from a cytoplasmic HeLa cell extract leads to a complete loss of 5S rRNA transcription without affecting tRNA synthesis. Transcription complexes for 5S RNA can no longer be assembled in such a zinc-depleted extract and this ability can be fu...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/12.23.8971

    authors: Wingender E,Dilloo D,Seifart KH

    更新日期:1984-12-11 00:00:00