Intercalating polycyclic aromatic hydrocarbon-DNA adducts poison DNA religation by Vaccinia topoisomerase and act as roadblocks to digestion by exonuclease III.

Abstract:

:Polycyclic aromatic hydrocarbon (PAH)-DNA adducts pervert the execution or fidelity of enzymatic DNA transactions and cause mutations and cancer. Here, we examine the effects of intercalating PAH-DNA adducts on the religation reaction of vaccinia DNA topoisomerase, a prototypal type IB topoisomerase (TopIB), and the 3' end-resection reaction of Escherichia coli exonuclease III (ExoIII), a DNA repair enzyme. Vaccinia TopIB forms a covalent DNA-(3'-phosphotyrosyl)-enzyme intermediate at a target site 5'-C(+5)C(+4)C(+3)T(+2)T(+1)p / N(-1) in duplex DNA. The rate of the forward cleavage reaction is suppressed to varying degrees by benzo[a]pyrene (BP) or benzo[c]phenanthrene (BPh) adducts at purine bases within the 3'-G(+5)G(+4)G(+3)A(+2)A(+1)T(-1)A(-2) sequence of the nonscissile strand. We report that BP adducts at the +1 and -2 N6-deoxyadenosine (dA) positions flanking the scissile phosphodiester slow the rate of DNA religation to a greater degree than they do the cleavage rate. By increasing the cleavage equilibrium constant > or = 10-fold, the BPdA adducts, which are intercalated via the major groove, act as TopIB poisons. With respect to ExoIII, we find that (i) single BPdA adducts act as durable roadblocks to ExoIII digestion, which is halted at sites 1 and 2 nucleotides prior to the modified base; (ii) single BPhdA adducts, which also intercalate via the major groove, elicit a transient pause prior to the lesion, which is eventually resected; and (iii) BPh adducts at N2-deoxyguanosine, which intercalate via the minor groove, are durable impediments to ExoIII digestion. These results highlight the sensitivity of repair outcomes to the structure of the PAH ring system and whether intercalation occurs via the major or minor groove.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Yakovleva L,Handy CJ,Yagi H,Sayer JM,Jerina DM,Shuman S

doi

10.1021/bi060158h

subject

Has Abstract

pub_date

2006-06-20 00:00:00

pages

7644-53

issue

24

eissn

0006-2960

issn

1520-4995

journal_volume

45

pub_type

杂志文章
  • Cell-cell recognition: specific binding of Microciona sponge aggregation factor to homotypic cells and the role of calcium ions.

    abstract::Previous studies have established that the mechanism of species-specific sponge cell reaggregation in vitro involves at least three components: a species-specific aggregation factor, its cell surface receptors, and Ca2+ ions. Here we report about the binding of Microciona 125I-labeled aggregation factor to cells and t...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00546a032

    authors: Jumblatt JE,Schlup V,Burger MM

    更新日期:1980-03-04 00:00:00

  • Characterization of human calcitonin fibrillation in aqueous urea solution by 1H NMR spectroscopy.

    abstract::The inhibitory effects of urea on the normally rapid fibrillation of human calcitonin (hCT) were investigated by 1H NMR. From subtle differences in the chemical shift of hCT in the presence and absence of urea, the occurrence of weak interactions between urea and hCT was confirmed. The chemical shifts on the NH and C ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi961013l

    authors: Kanaori K,Nosaka AY

    更新日期:1996-10-01 00:00:00

  • Structural Control of Nonnative Ligand Binding in Engineered Mutants of Phosphoenolpyruvate Carboxykinase.

    abstract::Protein engineering to alter recognition underlying ligand binding and activity has enormous potential. Here, ligand binding for Escherichia coli phosphoenolpyruvate carboxykinase (PEPCK), which converts oxaloacetate into CO2 and phosphoenolpyruvate as the first committed step in gluconeogenesis, was engineered to acc...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.8b00963

    authors: Tang HYH,Shin DS,Hura GL,Yang Y,Hu X,Lightstone FC,McGee MD,Padgett HS,Yannone SM,Tainer JA

    更新日期:2018-12-04 00:00:00

  • Systematic comparison of statistical analyses of electronic and vibrational circular dichroism for secondary structure prediction of selected proteins.

    abstract::The electronic (ultraviolet) circular dichroism (UVCD) and vibrational circular dichroism (VCD) of 20 proteins are systematically compared as to their relationship to the secondary structures of these proteins. The UVCD spectra are statistically treated by use of the same factor analysis methods used previously for VC...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00242a012

    authors: Pancoska P,Keiderling TA

    更新日期:1991-07-16 00:00:00

  • Monoclonal antibody to microtubule-associated STOP protein: affinity purification of neuronal STOP activity and comparison of antigen with activity in neuronal and nonneuronal cell extracts.

    abstract::Microtubules, ordinarily cold-labile structures, are made entirely resistant to cold temperature by the presence of substoichiometric amounts of STOP (stable tubule only polypeptide), a microtubule-associated protein. We have produced a monoclonal antibody which specifically recognizes a 145-kDa protein previously imp...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00428a064

    authors: Pirollet F,Rauch CT,Job D,Margolis RL

    更新日期:1989-01-24 00:00:00

  • Identification of the cyclosporin-binding site in P-glycoprotein.

    abstract::The binding site of cyclosporin A to P-glycoprotein was characterized by using a multidrug-resistant Chinese hamster ovary cell line. P-glycoprotein photolabeled with diazirine-cyclosporin A analogue was purified by a two-step process involving continuous elution electrophoresis followed by wheat germ agglutinin-agaro...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi981992c

    authors: Demeule M,Laplante A,Murphy GF,Wenger RM,Béliveau R

    更新日期:1998-12-22 00:00:00

  • Ternary complex crystal structures of glycogen phosphorylase with the transition state analogue nojirimycin tetrazole and phosphate in the T and R states.

    abstract::Catalysis by glycogen phosphorylase involves a mechanism in which binding of one substrate tightens the binding of the other substrate to produce a productive ternary enzyme-substrate complex. In this work the molecular basis for this synergism is probed in crystallographic studies on ternary complexes in which the gl...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi960072w

    authors: Mitchell EP,Withers SG,Ermert P,Vasella AT,Garman EF,Oikonomakos NG,Johnson LN

    更新日期:1996-06-11 00:00:00

  • Access to the active site of periplasmic nitrate reductase: insights from site-directed mutagenesis and zinc inhibition studies.

    abstract::The periplasmic nitrate reductase (NapAB), a member of the DMSO reductase superfamily, catalyzes the first step of the denitrification process in bacteria. In this heterodimer, a di-heme NapB subunit is associated to the catalytic NapA subunit that binds a [4Fe-4S] cluster and a bis(molybdopterin guanine dinucleotide)...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi700928m

    authors: Dementin S,Arnoux P,Frangioni B,Grosse S,Léger C,Burlat B,Guigliarelli B,Sabaty M,Pignol D

    更新日期:2007-08-28 00:00:00

  • Three small ribooligonucleotides with specific arginine sites.

    abstract::Arginine-binding RNA motifs are important to protein-RNA interaction and perhaps also for Archean biochemistry. Selection-amplification was used to isolate three RNAs that are eluted by free arginine from an L-arginine affinity column (Kd approximately 0.2-0.4 mM). The binding sites contain specific internal and bulge...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00072a002

    authors: Connell GJ,Illangesekare M,Yarus M

    更新日期:1993-06-01 00:00:00

  • Structural studies of acetylated and control inner core histones.

    abstract::The role of acetylation on the conformation and association state of the inner core histone octamer isolated from HeLa cells was examined. Preparation of suitable quantities of pure acetylated and control inner core histones from HeLa cells required the development of a new preparative procedure. The results from size...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00384a041

    authors: Prevelige PE Jr,Fasman GD

    更新日期:1987-05-19 00:00:00

  • Unexpected findings from target analysis of immunoglobulin E and its receptor.

    abstract::The membrane receptor for immunoglobulin E (IgE) and its ligand, IgE, were irradiated with high-energy electrons. Loss of binding activity was measured for each, and the size of the functional targets was assessed. In both cases, the target size was substantially smaller than the covalent structure of the molecule. Th...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00526a011

    authors: Fewtrell C,Kempner E,Poy G,Metzger H

    更新日期:1981-11-10 00:00:00

  • Evidence for the kinetic partitioning of polymerase activity on G-quadruplex DNA.

    abstract::We have investigated the action of the human DNA polymerase ε (hpol ε) and η (hpol η) catalytic cores on G-quadruplex (G4) DNA substrates derived from the promoter of the c-MYC proto-oncogene. The translesion enzyme hpol η exhibits a 6.2-fold preference for binding to G4 DNA over non-G4 DNA, while hpol ε binds both G4...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.5b00060

    authors: Eddy S,Maddukuri L,Ketkar A,Zafar MK,Henninger EE,Pursell ZF,Eoff RL

    更新日期:2015-05-26 00:00:00

  • Identification of a new P450 expressed in human lung: complete cDNA sequence, cDNA-directed expression, and chromosome mapping.

    abstract::A cDNA coding for a P450 expressed in human lung was isolated from a lambda gt11 library constructed from human lung mRNA using a cDNA probe to rat P450 IVA1. The cDNA-deduced amino acid sequence of this P450, designated IVB1, consisted of 511 amino acids and had a calculated molecular weight of 59,558. The IVB1 amino...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00446a014

    authors: Nhamburo PT,Gonzalez FJ,McBride OW,Gelboin HV,Kimura S

    更新日期:1989-10-03 00:00:00

  • Role of the tertiary nucleotides in the interaction of yeast phenylalanine tRNA with its cognate synthetase.

    abstract::In vitro transcription by T7 RNA polymerase was used to prepare 32 different mutations in the 21 nucleotides that participate in the 9 tertiary base pairs or triples of yeast tRNAPhe. The mutations were designed either to disrupt the tertiary interaction or to change the sequence without disrupting the structure by tr...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00462a014

    authors: Sampson JR,DiRenzo AB,Behlen LS,Uhlenbeck OC

    更新日期:1990-03-13 00:00:00

  • ATP-induced dimerization of the F0F1 ε subunit from Bacillus PS3: a hydrogen exchange-mass spectrometry study.

    abstract::F0F1 ATP synthase harnesses a transmembrane electrochemical gradient for the production of ATP. When operated in reverse, this multiprotein complex catalyzes ATP hydrolysis. In bacteria, the ε subunit is involved in regulating this ATPase activity. Also, ε is essential for coupling ATP hydrolysis (or synthesis) to pro...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi5004684

    authors: Rodriguez AD,Dunn SD,Konermann L

    更新日期:2014-06-24 00:00:00

  • Progressive development of a thrombin inhibitor binding site.

    abstract::The studies reported here were undertaken to determine whether the thrombin precursors prothrombin, prethrombin 1, prethrombin 2, and Meizo thrombin interact with the fluorescent, reversible thrombin inhibitor dansylarginine N,N-(3-ethyl-1,5-pentanediyl)amide (DAPA) [Nesheim, M. E., Prendergast, F. G., & Mann, K. G. (...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00539a003

    authors: Hibbard LS,Nesheim ME,Mann KG

    更新日期:1982-05-11 00:00:00

  • Folding of an enzyme into an active conformation while bound as peptidyl-tRNA to the ribosome.

    abstract::Rhodanese bound to bacterial ribosomes as peptidyl-tRNA can be folded into an enzymatically active conformation by generating C-terminal extensions of the wild-type enzyme. Rhodanese was synthesized by coupled transcription/translation in a cell-free Escherichia coli system from plasmids containing the coding sequence...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00044a003

    authors: Kudlicki W,Chirgwin J,Kramer G,Hardesty B

    更新日期:1995-11-07 00:00:00

  • Stability effects of increasing the hydrophobicity of solvent-exposed side chains in staphylococcal nuclease.

    abstract::A total of fifty single site surface phenylalanine substitution mutants have been made in the model protein staphylococcal nuclease. The fifty residues that were replaced with phenylalanine were chosen to give a broad sampling of solvent accessibility, secondary structure, and backbone conformations. The change in the...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi9725069

    authors: Schwehm JM,Kristyanne ES,Biggers CC,Stites WE

    更新日期:1998-05-12 00:00:00

  • Insights into the stability of native and partially folded states of ubiquitin: effects of cosolvents and denaturants on the thermodynamics of protein folding.

    abstract::The thermodynamics of the native<-->A state and native<-->unfolded transitions for ubiquitin have been characterized in detail using the denaturants methanol and guanidinium chloride (Gdn.HCl) both separately and in combination. Gdn.HCl destabilizes the partially folded alcohol-induced A state such that the effects of...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi010767j

    authors: Jourdan M,Searle MS

    更新日期:2001-08-28 00:00:00

  • Hepatitis C virus NS3 and simian virus 40 T antigen helicases displace streptavidin from 5'-biotinylated oligonucleotides but not from 3'-biotinylated oligonucleotides: evidence for directional bias in translocation on single-stranded DNA.

    abstract::Helicases are enzymes that use energy from nucleoside triphosphate hydrolysis to unwind double-stranded (ds) DNA, a process vital to virtually every phase of DNA metabolism. Helicases have been classified as either 5'-to-3' or 3'-to-5' on the basis of their ability to unwind duplex DNA adjacent to either a 5' or 3' si...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi012058b

    authors: Morris PD,Byrd AK,Tackett AJ,Cameron CE,Tanega P,Ott R,Fanning E,Raney KD

    更新日期:2002-02-19 00:00:00

  • Helix stop signals in proteins and peptides: the capping box.

    abstract::The alpha-helix [Pauling, L., Corey, R. B., & Branson, H. R. (1951) Proc. Natl. Acad. Sci. U.S.A. 37, 205-211] is a common motif in both proteins and peptides. Despite intense investigation, predictive understanding of helices is still lacking. A recent hypothesis [Presta, L. G., & Rose, G. D. (1988) Science 240, 1632...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00081a001

    authors: Harper ET,Rose GD

    更新日期:1993-08-03 00:00:00

  • Insertion of Argos sequences into the B-loop of epidermal growth factor results in a low-affinity ligand with strong agonistic activity.

    abstract::Recently, it has been shown that the activation of the Drosophila EGF receptor (DER) by its natural ligand Spitz is inhibited by Argos [Schweitzer, R., et al. (1995) Nature 376, 699-702]. Argos and Spitz both have an EGF-like domain which in the case of Argos differs from that of Spitz and other EGF receptor agonists ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi970227f

    authors: van de Poll ML,van Vugt MJ,Lenferink AE,van Zoelen EJ

    更新日期:1997-06-17 00:00:00

  • Formation of highly ordered multimers in G-quadruplexes.

    abstract::G-Rich DNA and RNA have a higher propensity to form G-quadruplex structures, but the presence of G-runs alone is not sufficient to prove that such sequences can form stable G-quadruplexes. While G-rich sequences are essential for G-quadruplex formation, not all G-rich sequences have the propensity to form G-quadruplex...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi500773c

    authors: Tóthová P,Krafčíková P,Víglaský V

    更新日期:2014-11-18 00:00:00

  • Inhibitors can activate proteases to catalyze the synthesis and hydrolysis of peptides.

    abstract::Competitive inhibitors can activate proteases (papain, trypsin, and cathepsin S) to catalyze the synthesis of peptide bonds and accelerate the hydrolysis of poor substrates (from 1 to 99%). Reaction mixtures contained intermediate molecules that were formed by the coupling of the inhibitor with the poor substrate. Thi...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi061910h

    authors: Schechter I,Ziv E

    更新日期:2006-12-12 00:00:00

  • Phenotypic regulation of the sphingosine 1-phosphate receptor miles apart by G protein-coupled receptor kinase 2.

    abstract::The evolutionarily conserved DRY motif at the end of the third helix of rhodopsin-like, class-A G protein-coupled receptors (GPCRs) is a major regulator of receptor stability, signaling activity, and β-arrestin-mediated internalization. Substitution of the DRY arginine with histidine in the human vasopressin receptor ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi501061h

    authors: Burczyk M,Burkhalter MD,Blätte T,Matysik S,Caron MG,Barak LS,Philipp M

    更新日期:2015-01-27 00:00:00

  • Multiple-step kinetic mechanisms of the ssDNA recognition process by human polymerase beta in its different ssDNA binding modes.

    abstract::The kinetics of human polymerase beta (pol beta) binding to the single-stranded DNA, in the (pol beta)(16) and (pol beta)(5) binding modes, that differ in the number of occluded nucleotide residues in the protein-DNA complexes, have been examined, using the fluorescence stopped-flow technique. This is the first determ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi011173j

    authors: Rajendran S,Jezewska MJ,Bujalowski W

    更新日期:2001-10-02 00:00:00

  • 6-(Methoxymethylene)penicillanic acid: inactivator of RTEM beta-lactamase from Escherichia coli.

    abstract::The Z and E isomers of 6-(methoxymethylene)-penicillanic acid have been synthesized, and their interaction with the RTEM beta-lactamase has been studied. The Z isomer is an inhibitor and an inactivator of the enzyme, and there is some similarity between its behavior and that of other mechanism-based inactivators such ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00319a025

    authors: Brenner DG,Knowles JR

    更新日期:1984-11-20 00:00:00

  • Cadmium-113 nuclear magnetic resonance studies of proteolytic fragments of calmodulin: assignment of strong and weak cation binding sites.

    abstract::Proteolytic fragments of bovine testis calmodulin were obtained by limited proteolysis with trypsin or thrombin. Cadmium-113 NMR studies showed that the tryptic fragment encompassing Ca2+ binding domains III and IV (TR2C) gave rise to a spectrum identical with that of the native protein. Two thrombic fragments contain...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00279a001

    authors: Andersson A,Forsén S,Thulin E,Vogel HJ

    更新日期:1983-05-10 00:00:00

  • Anticoagulantly active heparin-like molecules from vascular tissue.

    abstract::Mucopolysaccharides were isolated from calf cerebral microvasculature and calf aorta. The only complex carbohydrates that exhibited anticoagulant activity were heparin-like components. The biologic potencies of calf cerebral and aortic heparin-like species were 2.92 units/mg of anti-factor Xa activity and 2.85 units/m...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00303a023

    authors: Marcum JA,Rosenberg RD

    更新日期:1984-04-10 00:00:00

  • The dual-specific active site of 7,8-diaminopelargonic acid synthase and the effect of the R391A mutation.

    abstract::7,8-diaminopelargonic acid (DAPA) synthase (EC 2.6.1.62) is a pyridoxal phosphate (PLP)-dependent transaminase that catalyzes the transfer of the alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form DAPA in the antepenultimate step in the biosynthesis of biotin. The wild...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi026339a

    authors: Eliot AC,Sandmark J,Schneider G,Kirsch JF

    更新日期:2002-10-22 00:00:00