Human transcriptional coactivator PC4 stimulates DNA end joining and activates DSB repair activity.

Abstract:

:Human transcriptional coactivator PC4 is a highly abundant nuclear protein that is involved in diverse cellular processes ranging from transcription to chromatin organization. Earlier, we have shown that PC4, a positive activator of p53, overexpresses upon genotoxic insult in a p53-dependent manner. In the present study, we show that PC4 stimulates ligase-mediated DNA end joining irrespective of the source of DNA ligase. Pull-down assays reveal that PC4 helps in the association of DNA ends through its C-terminal domain. In vitro nonhomologous end-joining assays with cell-free extracts show that PC4 enhances the joining of noncomplementary DNA ends. Interestingly, we found that PC4 activates double-strand break (DSB) repair activity through stimulation of DSB rejoining in vivo. Together, these findings demonstrate PC4 as an activator of nonhomologous end joining and DSB repair activity.

journal_name

J Mol Biol

authors

Batta K,Yokokawa M,Takeyasu K,Kundu TK

doi

10.1016/j.jmb.2008.11.008

subject

Has Abstract

pub_date

2009-01-23 00:00:00

pages

788-99

issue

3

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(08)01413-7

journal_volume

385

pub_type

杂志文章
  • Preliminary X-ray diffraction studies of recombinant 19 kDa human fibroblast collagenase.

    abstract::Crystals of the catalytic domain of human fibroblast collagenase have been grown in the presence and absence of an inhibitor. Crystals of the inhibitor complex grew from 0.2 M ammonium sulfate and 15 to 30% PEG 8000 at 22 degrees C as bipyramids in the space group P6(2) or P6(4). Crystals of the unligated enzyme grew ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(94)90068-x

    authors: Hassell AM,Anderegg RJ,Weigl D,Milburn MV,Burkhart W,Smith GF,Graber P,Wells TN,Luther MA,Jordan SR

    更新日期:1994-03-11 00:00:00

  • Different binding modes of free and carrier-protein-coupled nicotine in a human monoclonal antibody.

    abstract::Nicotine is the principal addictive component of tobacco. Blocking its passage from the lung to the brain with nicotine-specific antibodies is a promising approach for the treatment of smoking addiction. We have determined the crystal structure of nicotine bound to the Fab fragment of a fully human monoclonal antibody...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2011.10.042

    authors: Tars K,Kotelovica S,Lipowsky G,Bauer M,Beerli RR,Bachmann MF,Maurer P

    更新日期:2012-01-06 00:00:00

  • Molecular mechanisms for viral mimicry of a human cytokine: activation of gp130 by HHV-8 interleukin-6.

    abstract::Kaposi's sarcoma-associated herpesvirus (KSHV, or HHV-8) encodes a pathogenic viral homologue of human interleukin-6 (IL-6). In contrast to human IL-6 (hIL-6), viral IL-6 (vIL-6) binds directly to, and activates, the shared human cytokine signaling receptor gp130 without the requirement for pre-complexation to a speci...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2003.10.070

    authors: Boulanger MJ,Chow DC,Brevnova E,Martick M,Sandford G,Nicholas J,Garcia KC

    更新日期:2004-01-09 00:00:00

  • Quasi-symmetry in the cryo-EM structure of EmrE provides the key to modeling its transmembrane domain.

    abstract::Small multidrug resistance (SMR) transporters contribute to bacterial resistance by coupling the efflux of a wide range of toxic aromatic cations, some of which are commonly used as antibiotics and antiseptics, to proton influx. EmrE is a prototypical small multidrug resistance transporter comprising four transmembran...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.08.072

    authors: Fleishman SJ,Harrington SE,Enosh A,Halperin D,Tate CG,Ben-Tal N

    更新日期:2006-11-17 00:00:00

  • Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs.

    abstract::The molecular chaperone Hsp90 is essential for the correct folding, maturation and activation of a diverse array of client proteins, including several key constituents of oncogenic processes. Hsp90 has become a focus of cancer research, since it represents a target for direct prophylaxis against multistep malignancy. ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2007.04.059

    authors: Phillips JJ,Yao ZP,Zhang W,McLaughlin S,Laue ED,Robinson CV,Jackson SE

    更新日期:2007-10-05 00:00:00

  • Amino acid acceptor identity switch of Escherichia coli tmRNA from alanine to histidine in vitro.

    abstract::According to a trans -translation model, tmRNA facilitates the resumption of translation that has been stalled on the ribosome with the 3' end of a terminator-less mRNA, to produce a chimera polypeptide of the nascent peptide and the tmRNA-encoding 11 amino acid-tag. The first alanine residue of the tag-sequence is en...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1999.2754

    authors: Nameki N,Tadaki T,Muto A,Himeno H

    更新日期:1999-05-28 00:00:00

  • Architecture of the ribosome-channel complex derived from native membranes.

    abstract::The mammalian Sec61 complex forms a protein translocation channel whose function depends upon its interaction with the ribosome and with membrane proteins of the endoplasmic reticulum (ER). To study these interactions, we determined structures of "native" ribosome-channel complexes derived from ER membranes. We find t...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2005.02.053

    authors: Ménétret JF,Hegde RS,Heinrich SU,Chandramouli P,Ludtke SJ,Rapoport TA,Akey CW

    更新日期:2005-04-29 00:00:00

  • Central domain of the positive control protein NifA and its role in transcriptional activation.

    abstract::The positive control protein NifA of Klebsiella pneumoniae activates transcription by RNA polymerase containing sigma 54 by catalysing open promoter complex formation. We show that the integrity of the putative ATP-binding pocket in the central domain of NifA is necessary for the positive control function of NifA, but...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(92)90921-6

    authors: Cannon W,Buck M

    更新日期:1992-05-20 00:00:00

  • Partially folded conformation of the (30-51) intermediate in the disulphide folding pathway of bovine pancreatic trypsin inhibitor. 1H and 15N resonance assignments and determination of backbone dynamics from 15N relaxation measurements.

    abstract::An analogue of the important folding intermediate of BPTI with only the disulphide bond between Cys30 and Cys51 has been characterized by 1H and 15N NMR techniques. In particular, the dynamics of the polypeptide backbone were characterized using (1H)-15N NOE and 15N T1 and T2 relaxation data. The intermediate is parti...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1993.1108

    authors: van Mierlo CP,Darby NJ,Keeler J,Neuhaus D,Creighton TE

    更新日期:1993-02-20 00:00:00

  • Variable electrostatic interaction between DNA and coat protein in filamentous bacteriophage assembly.

    abstract::A restriction fragment carrying the major coat protein gene (gene VIII) was excised from the DNA of the class I filamentous bacteriophage fd, which infects Escherichia coli. This fragment was cloned into the expression plasmid pKK223-3, where it came under the control of the tac promoter, generating plasmid pKf8P. Bac...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(88)90363-4

    authors: Rowitch DH,Hunter GJ,Perham RN

    更新日期:1988-12-05 00:00:00

  • From adenylate cyclase to guanylate cyclase. Mutational analysis of a change in substrate specificity.

    abstract::Adenylate and guanylate cyclases, having different but related substrates, are a paradigm for the study of substrate discrimination. A prokaryotic adenylate cyclase gene, phylogenetically related to eukaryotic counterparts, was screened for mutants remodelling the enzyme's specificity. In a first step, a mutant was se...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(92)90093-y

    authors: Beuve A,Danchin A

    更新日期:1992-06-20 00:00:00

  • The mechanism of transcriptional activation by the topologically DNA-linked sliding clamp of bacteriophage T4.

    abstract::Three viral proteins participate directly in transcription of bacteriophage T4 late genes: the sigma-family protein gp55 provides promoter recognition, gp33 is the co-activator, and gp45 is the activator of transcription; gp33 also represses transcription in the absence of gp45. Transcriptional activation by gp45, the...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/s0022-2836(02)00732-5

    authors: Kolesky SE,Ouhammouch M,Geiduschek EP

    更新日期:2002-08-30 00:00:00

  • Spectrum of spontaneously occurring mutations in the hprt gene of V79 Chinese hamster cells.

    abstract::A total of 76 independent spontaneous mutants in the hprt gene of V79 Chinese hamster cells have been analyzed. These mutants were obtained in two different laboratories, 17 and 59 mutants in sets 1 and 2, respectively, under different cell culture conditions. Mutation analysis was performed by amplification of hprt c...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(92)90979-t

    authors: Zhang LH,Vrieling H,van Zeeland AA,Jenssen D

    更新日期:1992-02-05 00:00:00

  • Three-dimensional crystal structure of human eosinophil cationic protein (RNase 3) at 1.75 A resolution.

    abstract::Eosinophil cationic protein (ECP; RNase 3) is a human ribonuclease found only in eosinophil leukocytes that belongs to the RNase A superfamily. This enzyme is bactericidal, helminthotoxic and cytotoxic to mammalian cells and tissues. The protein has been cloned, heterologously overexpressed, purified and crystallized....

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2000.3939

    authors: Mallorquí-Fernández G,Pous J,Peracaula R,Aymamí J,Maeda T,Tada H,Yamada H,Seno M,de Llorens R,Gomis-Rüth FX,Coll M

    更新日期:2000-07-28 00:00:00

  • Plasminogen activator inhibitor-2 is highly tolerant to P8 residue substitution--implications for serpin mechanistic model and prediction of nsSNP activities.

    abstract::The serine protease inhibitor (serpin) superfamily is involved in a wide range of cellular processes including fibrinolysis, angiogenesis, apoptosis, inflammation, metastasis and viral pathogenesis. Here, we investigate the unique mousetrap inhibition mechanism of serpins through saturation mutagenesis of the P8 resid...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2005.09.008

    authors: Di Giusto DA,Sutherland AP,Jankova L,Harrop SJ,Curmi PM,King GC

    更新日期:2005-11-11 00:00:00

  • The EGF-like protein dlk1 inhibits notch signaling and potentiates adipogenesis of mesenchymal cells.

    abstract::The EGF-like homeotic gene Dlk1 appears to function as an inhibitor of adipogenesis. Overexpression of Dlk1 prevents adipogenesis of 3T3-L1 cells. Dlk1-deficient mice are obese; however, adipose tissue still develops in Fc-dlk1 transgenic mice, suggesting that Dlk1 is not a strict inhibitor of adipogenesis. To clarify...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.10.043

    authors: Nueda ML,Baladrón V,Sánchez-Solana B,Ballesteros MA,Laborda J

    更新日期:2007-04-13 00:00:00

  • Hemoglobin allostery: new views on old players.

    abstract::Proteins are dynamic molecular machines whose structure and function are modulated by environmental perturbations and natural selection. Allosteric regulation, discovered in 1963 as a novel molecular mechanism of enzymatic adaptation [Monod, Changeux & Jacob (1963). J. Mol. Biol.6, 306-329], seems to be the leit motiv...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2012.12.018

    authors: Miele AE,Bellelli A,Brunori M

    更新日期:2013-05-13 00:00:00

  • Alternative splicing of an amino-terminal PEVK-like region generates multiple isoforms of Drosophila projectin.

    abstract::Drosophila projectin is an extremely large protein found within the muscle sarcomeric unit, parallel with the actin and myosin filaments. Projectin has been suggested as the elastic component of C-filaments in insect indirect flight muscles, which is consistent with its localization from the Z band to the tip of the A...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2001.5115

    authors: Southgate R,Ayme-Southgate A

    更新日期:2001-11-09 00:00:00

  • Identification of a minimal binding element within the T7 RNA polymerase promoter.

    abstract::The T7 RNA polymerase promoter has been proposed to contain two domains: the binding region upstream of position -5 is recognized through apparently traditional duplex contacts, while the catalytic domain downstream of position -5 is bound in a melted configuration. This model is tested by following polymerase binding...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1997.1350

    authors: Ujvári A,Martin CT

    更新日期:1997-11-07 00:00:00

  • Amino acid requirements for formation of the TGF-beta-latent TGF-beta binding protein complexes.

    abstract::Transforming growth factor beta (TGF-beta) is secreted primarily as a latent complex consisting of the TGF-beta homodimer, the TGF-beta propeptides (called the latency-associated protein or LAP) and the latent TGF-beta binding protein (LTBP). Mature TGF-beta remains associated with LAP by non-covalent interactions tha...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2004.10.039

    authors: Chen Y,Ali T,Todorovic V,O'leary JM,Kristina Downing A,Rifkin DB

    更新日期:2005-01-07 00:00:00

  • The oligomeric structure of vaccinia viral envelope protein A27L is essential for binding to heparin and heparan sulfates on cell surfaces: a structural and functional approach using site-specific mutagenesis.

    abstract::The soluble domain of the self-assembly vaccinia virus envelope protein A27L, sA27L-aa, consists of a flexible extended coil at the N terminus and a rigid hydrophobic coiled-coil region at the C terminus. In the former, a basic strip of 12 residues is responsible for binding to cell-surface heparan sulfates. Although ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2005.04.024

    authors: Ho Y,Hsiao JC,Yang MH,Chung CS,Peng YC,Lin TH,Chang W,Tzou DL

    更新日期:2005-06-24 00:00:00

  • Discerning the structure and energy of multiple transition states in protein folding using psi-analysis.

    abstract::We quantify the degree to which folding occurs along a complex landscape with structurally distinct pathways using psi-analysis in combination with a protein engineering method that identifies native, non-covalent polypeptide interactions and their relative populations at the rate-limiting step. By probing the proximi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2004.01.018

    authors: Krantz BA,Dothager RS,Sosnick TR

    更新日期:2004-03-19 00:00:00

  • Determining the critical nucleus and mechanism of fibril elongation of the Alzheimer's Abeta(1-40) peptide.

    abstract::We use a coarse-grained protein model to characterize the critical nucleus, structural stability, and fibril elongation propensity of Abeta(1-40) oligomers for the C(2x) and C(2z) quaternary forms proposed by solid-state NMR. By estimating equilibrium populations of structurally stable and unstable protofibrils, we de...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.10.011

    authors: Fawzi NL,Okabe Y,Yap EH,Head-Gordon T

    更新日期:2007-01-12 00:00:00

  • Single molecule force spectroscopy of spectrin repeats: low unfolding forces in helix bundles.

    abstract::Spectrin repeats fold into triple helical coiled-coils comprising approximately 106 amino acid residues. Using an AFM-related technique we measured the force required to mechanically unfold these repeats to be 25 to 35 pN. Under tension, individual spectrin repeats unfold independently and in an all-or-none process. T...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1998.2466

    authors: Rief M,Pascual J,Saraste M,Gaub HE

    更新日期:1999-02-19 00:00:00

  • Thermodynamic and kinetic characterization of ligand binding to the purine riboswitch aptamer domain.

    abstract::Riboswitches are cis-acting genetic regulatory elements found commonly in bacterial mRNAs that consist of a metabolite-responsive aptamer domain coupled to a regulatory switch. Purine riboswitches respond to intracellular concentrations of either adenine or guanine/hypoxanthine to control gene expression. The aptamer ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.04.003

    authors: Gilbert SD,Stoddard CD,Wise SJ,Batey RT

    更新日期:2006-06-09 00:00:00

  • Ligand-induced conformational changes via flexible linkers in the amino-terminal region of the inositol 1,4,5-trisphosphate receptor.

    abstract::Cytoplasmic Ca2+ signals are highly regulated by various ion transporters, including the inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R), which functions as a Ca2+ release channel on the endoplasmic reticulum membrane. Crystal structures of the two N-terminal regulatory regions from type 1 IP(3)R have been repo...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2007.08.057

    authors: Chan J,Whitten AE,Jeffries CM,Bosanac I,Mal TK,Ito J,Porumb H,Michikawa T,Mikoshiba K,Trewhella J,Ikura M

    更新日期:2007-11-09 00:00:00

  • Stabilization of native protein fold by intein-mediated covalent cyclization.

    abstract::A mutant version of the N-terminal domain of Escherichia coli DnaB helicase was used as a model system to assess the stabilization against unfolding gained by covalent cyclization. Cyclization was achieved in vivo by formation of an amide bond between the N and C termini with the help of a split mini-intein. Linear an...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2004.12.037

    authors: Williams NK,Liepinsh E,Watt SJ,Prosselkov P,Matthews JM,Attard P,Beck JL,Dixon NE,Otting G

    更新日期:2005-03-04 00:00:00

  • NMR solution structure of Mob1, a mitotic exit network protein and its interaction with an NDR kinase peptide.

    abstract::Proteins of the Mob1/phocein family are found in all eukaryotic cells. In yeast, they are activating subunits of Dbf2-related protein kinases involved in cell cycle control. Despite the wide occurrence of these proteins, their biological functions remain poorly understood. Here we report the solution structure of the ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2004.01.010

    authors: Ponchon L,Dumas C,Kajava AV,Fesquet D,Padilla A

    更新日期:2004-03-12 00:00:00

  • A comparison of the pH, urea, and temperature-denatured states of barnase by heteronuclear NMR: implications for the initiation of protein folding.

    abstract::The denatured states of barnase that are induced by urea, acid, and high temperature and acid have been assigned and characterised by high resolution heteronuclear NMR. The assignment was completed using a combination of triple-resonance and magnetisation-transfer methods. The latter was facilitated by selecting a sui...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1995.0618

    authors: Arcus VL,Vuilleumier S,Freund SM,Bycroft M,Fersht AR

    更新日期:1995-11-24 00:00:00

  • Structural comparison of cuticle and interstitial collagens from annelids living in shallow sea-water and at deep-sea hydrothermal vents.

    abstract::Two types of annelid collagens of different sizes were purified, one from acetic acid extracts of the cuticle (length 2.5 microns) and the other, after pepsin digestion, from interstitial spaces of the body wall (0.3 micron). They were obtained from Alvinella pompejana, Alvinella caudata and Paralvinella grasslei coll...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1994.0084

    authors: Gaill F,Mann K,Wiedemann H,Engel J,Timpl R

    更新日期:1995-02-17 00:00:00