Ascorbate acts as a highly potent inducer of chromate mutagenesis and clastogenesis: linkage to DNA breaks in G2 phase by mismatch repair.

Abstract:

:Here we examined the role of cellular vitamin C in genotoxicity of carcinogenic chromium(VI) that requires reduction to induce DNA damage. In the presence of ascorbate (Asc), low 0.2-2 microM doses of Cr(VI) caused 10-15 times more chromosomal breakage in primary human bronchial epithelial cells or lung fibroblasts. DNA double-strand breaks (DSB) were preferentially generated in G2 phase as detected by colocalization of H2AX and 53BP1 foci in cyclin B1-expressing cells. Asc dramatically increased the formation of centromere-negative micronuclei, demonstrating that induced DSB were inefficiently repaired. DSB in G2 cells were caused by aberrant mismatch repair of Cr damage in replicated DNA, as DNA polymerase inhibitor aphidicolin and silencing of MSH2 or MLH1 by shRNA suppressed induction of H2AX and micronuclei. Cr(VI) was also up to 10 times more mutagenic in cells containing Asc. Increasing Asc concentrations generated progressively more mutations and DSB, revealing the genotoxic potential of otherwise nontoxic Cr(VI) doses. Asc amplified genotoxicity of Cr(VI) by altering the spectrum of DNA damage, as total Cr-DNA binding was unchanged and post-Cr loading of Asc exhibited no effects. Collectively, these studies demonstrated that Asc-dependent metabolism is the main source of genotoxic and mutagenic damage in Cr(VI)-exposed cells.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Reynolds M,Stoddard L,Bespalov I,Zhitkovich A

doi

10.1093/nar/gkl1069

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

465-76

issue

2

eissn

0305-1048

issn

1362-4962

pii

gkl1069

journal_volume

35

pub_type

杂志文章
  • Different conformational families of pyrimidine.purine.pyrimidine triple helices depending on backbone composition.

    abstract::Different helical conformations of DNA (D), RNA (R), and DNA.RNA (DR) hybrid double and triple helices have been detected using affinity cleavage analysis. Synthetic methods were developed to attach EDTA.Fe to a single nucleotide on RNA as well as DNA oligonucleotides. Cleavage patterns generated by a localized diffus...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/22.14.2837

    authors: Han H,Dervan PB

    更新日期:1994-07-25 00:00:00

  • pBR322 DNA inhibits simian virus 40 gene expression in Xenopus laevis oocytes.

    abstract::SV40 DNA form I is expressed efficiently after its injection into the nuclei of Xenopus laevis oocytes, resulting in the synthesis of RNA and protein products of both viral late and early transcription units. However it was observed that injection of SV40 genes cloned into pBR322 or related plasmids yielded vastly red...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/15.4.1579

    authors: Michaeli T,Prives C

    更新日期:1987-02-25 00:00:00

  • Significant expansion of the REST/NRSF cistrome in human versus mouse embryonic stem cells: potential implications for neural development.

    abstract::Recent studies have employed cross-species comparisons of transcription factor binding, reporting significant regulatory network 'rewiring' between species. Here, we address how a transcriptional repressor targets and regulates neural genes differentially between human and mouse embryonic stem cells (ESCs). We find th...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv514

    authors: Rockowitz S,Zheng D

    更新日期:2015-07-13 00:00:00

  • ComplexContact: a web server for inter-protein contact prediction using deep learning.

    abstract::ComplexContact (http://raptorx2.uchicago.edu/ComplexContact/) is a web server for sequence-based interfacial residue-residue contact prediction of a putative protein complex. Interfacial residue-residue contacts are critical for understanding how proteins form complex and interact at residue level. When receiving a pa...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gky420

    authors: Zeng H,Wang S,Zhou T,Zhao F,Li X,Wu Q,Xu J

    更新日期:2018-07-02 00:00:00

  • Complex impact of DNA methylation on transcriptional dysregulation across 22 human cancer types.

    abstract::Accumulating evidence has demonstrated that transcriptional regulation is affected by DNA methylation. Understanding the perturbation of DNA methylation-mediated regulation between transcriptional factors (TFs) and targets is crucial for human diseases. However, the global landscape of DNA methylation-mediated transcr...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa041

    authors: Wang Z,Yin J,Zhou W,Bai J,Xie Y,Xu K,Zheng X,Xiao J,Zhou L,Qi X,Li Y,Li X,Xu J

    更新日期:2020-03-18 00:00:00

  • Developmentally regulated and erythroid-specific expression of the human embryonic beta-globin gene in transgenic mice.

    abstract::Transgenic mice have proven to be an effective expression system for studying developmental control of the human fetal and adult beta-globin genes. In the current work we are interested in developing the transgenic mouse system for the study of the human embryonic beta-globin gene, epsilon. An epsilon-globin gene cons...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/18.18.5465

    authors: Shih DM,Wall RJ,Shapiro SG

    更新日期:1990-09-25 00:00:00

  • Influence of template inactivators on the binding of DNA polymerase to DNA.

    abstract::The agents daunomycin, ethidium bromide, distamycin A and cytochrome c inhibit DNA dependent DNA polymerase I (E. coli) reaction competitively to DNA. The influence of these template inactivators on the binding of DNA polymerase to native as well as denatured DNA has been determined by affinity chromatography. Cytochr...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/1.1.63

    authors: Müller WE,Obermeier J,Totsuka A,Zahn RK

    更新日期:1974-01-01 00:00:00

  • Proton magnetic resonance studies of ultraviolet-irradiated apurinic acid.

    abstract::In apurinic acid, a single-stranded polydeoxyribonucleotide easily obtained upon depurination of DNA, the proton resonances arising from thymine and cytosine are readily observable in aqueous solution of 25 degrees C. Two methyl thymine resonances, centered at 1.88 ppm and separated by 0.045 ppm, are observed. We attr...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/1.8.999

    authors: Rahn RO,Schleich T

    更新日期:1974-08-01 00:00:00

  • Not1 mediates recruitment of the deadenylase Caf1 to mRNAs targeted for degradation by tristetraprolin.

    abstract::The carbon catabolite repressor protein 4 (Ccr4)-Negative on TATA (Not) complex controls gene expression at two levels. In the nucleus, it regulates the basal transcription machinery, nuclear receptor-mediated transcription and histone modifications. In the cytoplasm, the complex is required for messenger RNA (mRNA) t...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr011

    authors: Sandler H,Kreth J,Timmers HT,Stoecklin G

    更新日期:2011-05-01 00:00:00

  • Open complex formation during transcription initiation at the Escherichia coli galP1 promoter: the role of the RNA polymerase alpha subunit at promoters lacking an UP-element.

    abstract::We have studied the role of the C-terminal domain of the alpha subunit (alphaCTD) of Escherichia coli RNA polymerase during transcription initiation at promoters lacking an UP-element. The temperature requirement for open complex formation was used as an indication of the kinetics of this process. We have previously s...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/27.9.2051

    authors: Burns HD,Ishihama A,Minchin SD

    更新日期:1999-05-01 00:00:00

  • RB signaling prevents replication-dependent DNA double-strand breaks following genotoxic insult.

    abstract::Cell cycle checkpoints induced by DNA damage play an integral role in preservation of genomic stability by allowing cells to limit the propagation of deleterious mutations. The retinoblastoma tumor suppressor (RB) is crucial for the maintenance of the DNA damage checkpoint function because it elicits cell cycle arrest...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkg919

    authors: Bosco EE,Mayhew CN,Hennigan RF,Sage J,Jacks T,Knudsen ES

    更新日期:2004-01-02 00:00:00

  • Effects of codon usage on gene expression are promoter context dependent.

    abstract::Codon usage bias is a universal feature of all genomes. Although codon usage has been shown to regulate mRNA and protein levels by influencing mRNA decay and transcription in eukaryotes, little or no genome-wide correlations between codon usage and mRNA levels are detected in mammalian cells, raising doubt on the sign...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa1253

    authors: Yang Q,Lyu X,Zhao F,Liu Y

    更新日期:2021-01-25 00:00:00

  • The Signal Recognition Particle Database (SRPDB).

    abstract::The signal recognition particle database (SRPDB) is located at the University of Texas Health Science Center at Tyler and includes tabulations of SRP RNA, SRP protein and SRP receptor sequences. The sequences are annotated with links to the primary databases. They are ordered alphabetically or phylogenetically and are...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/27.1.169

    authors: Samuelsson T,Zwieb C

    更新日期:1999-01-01 00:00:00

  • BRENDA, the enzyme database: updates and major new developments.

    abstract::BRENDA (BRaunschweig ENzyme DAtabase) represents a comprehensive collection of enzyme and metabolic information, based on primary literature. The database contains data from at least 83,000 different enzymes from 9800 different organisms, classified in approximately 4200 EC numbers. BRENDA includes biochemical and mol...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkh081

    authors: Schomburg I,Chang A,Ebeling C,Gremse M,Heldt C,Huhn G,Schomburg D

    更新日期:2004-01-01 00:00:00

  • Characterization of a cAMP responsive transcription factor, Cmr (Rv1675c), in TB complex mycobacteria reveals overlap with the DosR (DevR) dormancy regulon.

    abstract::Mycobacterium tuberculosis (Mtb) Cmr (Rv1675c) is a CRP/FNR family transcription factor known to be responsive to cAMP levels and during macrophage infections. However, Cmr's DNA binding properties, cellular targets and overall role in tuberculosis (TB) complex bacteria have not been characterized. In this study, we u...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv889

    authors: Ranganathan S,Bai G,Lyubetskaya A,Knapp GS,Peterson MW,Gazdik M,C Gomes AL,Galagan JE,McDonough KA

    更新日期:2016-01-08 00:00:00

  • A mostly traditional approach improves alignment of bisulfite-converted DNA.

    abstract::Cytosines in genomic DNA are sometimes methylated. This affects many biological processes and diseases. The standard way of measuring methylation is to use bisulfite, which converts unmethylated cytosines to thymines, then sequence the DNA and compare it to a reference genome sequence. We describe a method for the cri...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks275

    authors: Frith MC,Mori R,Asai K

    更新日期:2012-07-01 00:00:00

  • SUPERFAMILY--sophisticated comparative genomics, data mining, visualization and phylogeny.

    abstract::SUPERFAMILY provides structural, functional and evolutionary information for proteins from all completely sequenced genomes, and large sequence collections such as UniProt. Protein domain assignments for over 900 genomes are included in the database, which can be accessed at http://supfam.org/. Hidden Markov models ba...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn762

    authors: Wilson D,Pethica R,Zhou Y,Talbot C,Vogel C,Madera M,Chothia C,Gough J

    更新日期:2009-01-01 00:00:00

  • Dual enhancer activities of the cyclic-AMP responsive element with cell type and promoter specificity.

    abstract::The role of the cyclic-AMP (cAMP) responsive element (CRE) in eukaryotic gene transcription was investigated in several cell lines transfected by constructs containing the chloramphenicol acetyltransferase (CAT) gene linked to the three different promoters, simian virus (SV) 40, human c-Ha-ras-1, or chicken beta-actin...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/17.4.1521

    authors: Kanei-Ishii C,Ishii S

    更新日期:1989-02-25 00:00:00

  • M-Coffee: combining multiple sequence alignment methods with T-Coffee.

    abstract::We introduce M-Coffee, a meta-method for assembling multiple sequence alignments (MSA) by combining the output of several individual methods into one single MSA. M-Coffee is an extension of T-Coffee and uses consistency to estimate a consensus alignment. We show that the procedure is robust to variations in the choice...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkl091

    authors: Wallace IM,O'Sullivan O,Higgins DG,Notredame C

    更新日期:2006-03-23 00:00:00

  • Stability of HPRT marker gene expression at different gene-targeted loci: observing and overcoming a position effect.

    abstract::For sophisticated gene targeting procedures requiring two sequential selective steps to operate efficiently it is essential that the marker genes used are not prone to position effects. The double replacement gene targeting procedure, to produce mice with subtle gene alterations, is based on the use of hypoxanthine ph...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.19.3937

    authors: Melton DW,Ketchen AM,Selfridge J

    更新日期:1997-10-01 00:00:00

  • Cloning and characterization of a human DEAH-box RNA helicase, a functional homolog of fission yeast Cdc28/Prp8.

    abstract::During the splicing process, spliceosomal snRNAs undergo numerous conformational rearrangements that appear to be catalyzed by proteins belonging to the DEAD/H-box superfamily of RNA helicases. We have cloned a new RNA helicase gene, designated DBP2 (DEAH-boxprotein), homologous to the Schizosaccaromyces pombe cdc28(+...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/26.9.2063

    authors: Imamura O,Saiki K,Tani T,Ohshima Y,Sugawara M,Furuichi Y

    更新日期:1998-05-01 00:00:00

  • Kinetic analysis of N-alkylaryl carboxamide hexitol nucleotides as substrates for evolved polymerases.

    abstract::Six 1',5'-anhydrohexitol uridine triphosphates were synthesized with aromatic substitutions appended via a carboxamide linker to the 5-position of their bases. An improved method for obtaining such 5-substituted hexitol nucleosides and nucleotides is described. The incorporation profile of the nucleotide analogues int...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz008

    authors: Renders M,Dumbre S,Abramov M,Kestemont D,Margamuljana L,Largy E,Cozens C,Vandenameele J,Pinheiro VB,Toye D,Frère JM,Herdewijn P

    更新日期:2019-03-18 00:00:00

  • COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples.

    abstract::An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the map...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkw026

    authors: Yamagata K,Yamanishi A,Kokubu C,Takeda J,Sese J

    更新日期:2016-05-05 00:00:00

  • CisMols Analyzer: identification of compositionally similar cis-element clusters in ortholog conserved regions of coordinately expressed genes.

    abstract::Combinatorial interactions of sequence-specific trans-acting factors with localized genomic cis-element clusters are the principal mechanism for regulating tissue-specific and developmental gene expression. With the emergence of expanding numbers of genome-wide expression analyses, the identification of the cis-elemen...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gki486

    authors: Jegga AG,Gupta A,Gowrisankar S,Deshmukh MA,Connolly S,Finley K,Aronow BJ

    更新日期:2005-07-01 00:00:00

  • Interference activity of a minimal Type I CRISPR-Cas system from Shewanella putrefaciens.

    abstract::Type I CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas (CRISPR-associated) systems exist in bacterial and archaeal organisms and provide immunity against foreign DNA. The Cas protein content of the DNA interference complexes (termed Cascade) varies between different CRISPR-Cas subtypes. A minima...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv882

    authors: Dwarakanath S,Brenzinger S,Gleditzsch D,Plagens A,Klingl A,Thormann K,Randau L

    更新日期:2015-10-15 00:00:00

  • The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway.

    abstract::Nonsense-mediated mRNA decay (NMD) is a molecular pathway of mRNA surveillance that ensures rapid degradation of mRNAs containing premature translation termination codons (PTCs) in eukaryotes. NMD has been shown to also regulate normal gene expression and thus emerged as one of the key post-transcriptional mechanisms ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkm461

    authors: Viegas MH,Gehring NH,Breit S,Hentze MW,Kulozik AE

    更新日期:2007-01-01 00:00:00

  • An integrated, structure- and energy-based view of the genetic code.

    abstract::The principles of mRNA decoding are conserved among all extant life forms. We present an integrative view of all the interaction networks between mRNA, tRNA and rRNA: the intrinsic stability of codon-anticodon duplex, the conformation of the anticodon hairpin, the presence of modified nucleotides, the occurrence of no...

    journal_title:Nucleic acids research

    pub_type: 杂志文章,评审

    doi:10.1093/nar/gkw608

    authors: Grosjean H,Westhof E

    更新日期:2016-09-30 00:00:00

  • TcSNP: a database of genetic variation in Trypanosoma cruzi.

    abstract::The TcSNP database (http://snps.tcruzi.org) integrates information on genetic variation (polymorphisms and mutations) for different stocks, strains and isolates of Trypanosoma cruzi, the causative agent of Chagas disease. The database incorporates sequences (genes from the T. cruzi reference genome, mRNAs, ESTs and ge...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn874

    authors: Ackermann AA,Carmona SJ,Agüero F

    更新日期:2009-01-01 00:00:00

  • DNA-protein interactions in the Drosophila virilis mitochondrial chromosome.

    abstract::The location of proteins on the mitochondrial DNA (mtDNA) of Drosophila virilis was investigated by Me3 psoralen photoreaction of mitochondria isolated from embryos. After photoreaction the mtDNA was purified and the pattern of DNA cross-linking was determined by electron microscopy of the DNA under totally denaturing...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/12.4.1991

    authors: Pardue ML,Fostel JM,Cech TR

    更新日期:1984-02-24 00:00:00

  • Experimental identification and analysis of macronuclear non-coding RNAs from the ciliate Tetrahymena thermophila.

    abstract::The ciliate Tetrahymena thermophila is an important eukaryotic model organism that has been used in pioneering studies of general phenomena, such as ribozymes, telomeres, chromatin structure and genome reorganization. Recent work has shown that Tetrahymena has many classes of small RNA molecules expressed during veget...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr792

    authors: Andersen KL,Nielsen H

    更新日期:2012-02-01 00:00:00