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The EMBO Journal

Cover image for Vol. 30 Issue 19

October 5, 2011

Volume 30, Issue 19

Pages 3875–4111

  1. Have you seen?

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    3. Review
    4. Article
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      Rac1 activation comes full circle (pages 3875–3877)

      Marc Symons

      Article first published online: 5 OCT 2011 | DOI: 10.1038/emboj.2011.330

      Precise spatiotemporal control of the Rac1 GTPase coordinates actin dynamics. A positive feedback loop involving the actin-binding protein coronin and the Rac regulators ArhGEF7, Pak1 and RhoGDI promotes Rac activity and actin polymerization at the cell cortex.

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      G4 DNA: at risk in the genome (pages 3878–3879)

      Luther Davis and Nancy Maizels

      Article first published online: 5 OCT 2011 | DOI: 10.1038/emboj.2011.342

      A study in this issue offers new evidence for G-quadruplex (G4) DNA structure formation in vivo and its contribution to genomic instability, and identifies specific cellular mechanisms to cope with such threats.

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      von Willebrand factor folds into a bouquet (pages 3880–3881)

      Volker Gerke

      Article first published online: 5 OCT 2011 | DOI: 10.1038/emboj.2011.321

      The healing of blood vessel injury requires release of von Willebrand factor (vWF). New structures explain the pH-dependent transition of tightly packed to extended forms of multimeric vWF.

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      Starting from scratch: de novo kinetochore assembly in vertebrates (pages 3882–3884)

      Sarion R Bowers and Barbara G Mellone

      Article first published online: 6 SEP 2011 | DOI: 10.1038/emboj.2011.329

      Recent studies in Cell and Nature shed light on how the kinetochore is recruited to centromeres during cell division, using elegant cell-based and in vitro assays to recapitulate kinetochore formation at artificial centromeres.

  2. Review

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    3. Review
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      FOXA1: master of steroid receptor function in cancer (pages 3885–3894)

      Michael A Augello, Theresa E Hickey and Karen E Knudsen

      Article first published online: 20 SEP 2011 | DOI: 10.1038/emboj.2011.340

      This review highlights recent progress on the predominant role of FOXA1 in nuclear hormone receptor activity with an emphasis on human breast and prostate cancer.

  3. Article

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    3. Review
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      Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation (pages 3895–3912)

      Ariel Quintana, Mathias Pasche, Christian Junker, Dalia Al-Ansary, Heiko Rieger, Carsten Kummerow, Lucia Nuñez, Carlos Villalobos, Paul Meraner, Ute Becherer, Jens Rettig, Barbara A Niemeyer and Markus Hoth

      Article first published online: 16 AUG 2011 | DOI: 10.1038/emboj.2011.289

      T-cell polarization and the formation of the immunological synapse (IS) are essential for calcium-dependent T-cell activation. Here, the findings report on the interplay between ORAI channels, mitochondria and PMCA at the IS to generate local Ca2+ microdomains that contribute to NFAT activity and T-cell activation.

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      Coronin 1A promotes a cytoskeletal-based feedback loop that facilitates Rac1 translocation and activation (pages 3913–3927)

      Antonio Castro-Castro, Virginia Ojeda, María Barreira, Vincent Sauzeau, Inmaculada Navarro-Lérida, Olivia Muriel, José R Couceiro, Felipe X Pimentel-Muíños, Miguel A del Pozo and Xosé R Bustelo

      Article first published online: 26 AUG 2011 | DOI: 10.1038/emboj.2011.310

      The Rac1 GTPase promotes cortical actin accumulation. Coronin 1a and the Rac1 GEF ArhGEF7 bind polymerized actin and promote Rac1 activation, thus establishing a positive feedback circuit to regulate the localization and activity of Rac1.

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      The kinesin-13 MCAK has an unconventional ATPase cycle adapted for microtubule depolymerization (pages 3928–3939)

      Claire T Friel and Jonathon Howard

      Article first published online: 26 AUG 2011 | DOI: 10.1038/emboj.2011.290

      Most kinesins move directionally along microtubules, but MCAK instead depolymerizes them. This study analyses the ATPase cycle of MCAK, identifying unusual kinetic features that fit with its unconventional activity.

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      Mechanism of transcriptional repression at a bacterial promoter by analysis of single molecules (pages 3940–3946)

      Alvaro Sanchez, Melisa L Osborne, Larry J Friedman, Jane Kondev and Jeff Gelles

      Article first published online: 9 AUG 2011 | DOI: 10.1038/emboj.2011.273

      Colocalization of single-molecule spectroscopy is used to resolve the mechanism of transcriptional inhibition by the Lac repressor by showing that it binds to the promoter and prevents recruitment of RNA polymerase and open complex formation.

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      H3K27 demethylation by JMJD3 at a poised enhancer of anti-apoptotic gene BCL2 determines ERα ligand dependency (pages 3947–3961)

      Amy Svotelis, Stéphanie Bianco, Jason Madore, Gabrielle Huppé, Alexei Nordell-Markovits, Anne-Marie Mes-Masson and Nicolas Gévry

      Article first published online: 12 AUG 2011 | DOI: 10.1038/emboj.2011.284

      Oestrogen receptor α cooperates with a histone demethylase to erase repressive chromatin marks and activate transcription in oestrogen-dependent cells, a mechanism dispensable in oestrogen-independent cells due to PI3K-mediated histone methyltransferase inactivation.

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      Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer (pages 3962–3976)

      Biswajyoti Sahu, Marko Laakso, Kristian Ovaska, Tuomas Mirtti, Johan Lundin, Antti Rannikko, Anna Sankila, Juha-Pekka Turunen, Mikael Lundin, Juho Konsti, Tiina Vesterinen, Stig Nordling, Olli Kallioniemi, Sampsa Hautaniemi and Olli A Jänne

      Article first published online: 13 SEP 2011 | DOI: 10.1038/emboj.2011.328

      Combining ChIP-seq, bioinformatic and functional data, this study addresses the genome-wide properties of the androgen receptor (AR). Modulation of the AR-pioneering factor FoxA1 results in a new picture distinguishing FoxA1-dependent from FoxA1-independent AR-genomic loci and the discovery of a third class that becomes reprogrammed by FoxA1 depletion.

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      A systematic analysis of Drosophila TUDOR domain-containing proteins identifies Vreteno and the Tdrd12 family as essential primary piRNA pathway factors (pages 3977–3993)

      Dominik Handler, Daniel Olivieri, Maria Novatchkova, Franz Sebastian Gruber, Katharina Meixner, Karl Mechtler, Alexander Stark, Ravi Sachidanandam and Julius Brennecke

      Article first published online: 23 AUG 2011 | DOI: 10.1038/emboj.2011.308

      The piRNA pathway plays an important role in germline development. This systematic screen of TUDOR domain-containing proteins in Drosophila describes roles for Vreteno, Brother of Yb and Sister of Yb in the somatic and/or germline piRNA pathways.

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      Nucleophosmin deposition during mRNA 3′ end processing influences poly(A) tail length (pages 3994–4005)

      Fumihiko Sagawa, Hend Ibrahim, Angela L Morrison, Carol J Wilusz and Jeffrey Wilusz

      Article first published online: 5 AUG 2011 | DOI: 10.1038/emboj.2011.272

      Nucleophosmin (NPM1) has been implicated in many nuclear activities involving DNA and RNA. Here, NPM1 is deposited on cellular mRNAs, interacts with the CPSF processing factor and has a role in regulating poly(A) tail length.

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      A cluster of ribosome synthesis factors regulate pre-rRNA folding and 5.8S rRNA maturation by the Rat1 exonuclease (pages 4006–4019)

      Sander Granneman, Elisabeth Petfalski and David Tollervey

      Article first published online: 2 AUG 2011 | DOI: 10.1038/emboj.2011.256

      Ribosome biogenesis involves a number of pre-rRNA cleavage events. This study characterizes the pre-rRNA interaction sites of the ribosome synthesis factors Cic1, Erb1, Nop7, Nop12, Nop15 and Nop4 and the 5′-exonuclease Rat1 and their role in 5.8S rRNA processing.

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      Assembly of Saccharomyces cerevisiae 60S ribosomal subunits: role of factors required for 27S pre-rRNA processing (pages 4020–4032)

      Aarti Sahasranaman, Jill Dembowski, John Strahler, Philip Andrews, Janine Maddock and John L Woolford Jr

      Article first published online: 16 SEP 2011 | DOI: 10.1038/emboj.2011.338

      The molecular mechanism of ribosome biogenesis is still ill-understood. This study characterizes 27SA3 pre-rRNA processing in detail. All known A3 processing factors associate with preribosomes well before their requirement and establish a neighbourhood that stabilizes functional preribosomes containing 27S pre-rRNAs.

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      G-quadruplex-induced instability during leading-strand replication (pages 4033–4046)

      Judith Lopes, Aurèle Piazza, Rodrigo Bermejo, Barry Kriegsman, Arianna Colosio, Marie-Paule Teulade-Fichou, Marco Foiani and Alain Nicolas

      Article first published online: 26 AUG 2011 | DOI: 10.1038/emboj.2011.316

      G-rich nucleic acid stretches can form secondary structures that require dedicated resolving helicases, making their in vivo occurrence likely to affect genome stability. A defined G-quadruplex-forming sequence indeed perturbs replication in yeast, in a striking orientation-dependent manner.

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      Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication (pages 4047–4058)

      Raghav Chawla, Sophie Redon, Christina Raftopoulou, Harry Wischnewski, Sarantis Gagos and Claus M Azzalin

      Article first published online: 9 AUG 2011 | DOI: 10.1038/emboj.2011.280

      UPF1, a helicase/ATPase with roles in mRNA surveillance that is also found at human telomeres, directly interacts with telomerase and a shelterin component, and involved selectively in telomere leading-strand replication.

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      RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interactions with a distal regulatory element (pages 4059–4070)

      Elena Levantini, Sanghoon Lee, Hanna S Radomska, Christopher J Hetherington, Meritxell Alberich-Jorda, Giovanni Amabile, Pu Zhang, David A Gonzalez, Junyan Zhang, Daniela S Basseres, Nicola K Wilson, Steffen Koschmieder, Gang Huang, Dong-Er Zhang, Alexander K Ebralidze, Constanze Bonifer, Yutaka Okuno, Bertie Gottgens and Daniel G Tenen

      Article first published online: 26 AUG 2011 | DOI: 10.1038/emboj.2011.285

      This study reveals molecular details of RUNX1 function in haematopoiesis. Employing various in vivo genetic models and chromatin conformation capture (3C) assays in HSCs, RUNX1 is shown to regulate CD34 expression by looping of a newly characterized distal regulatory element to the core promoter.

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      A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories (pages 4071–4083)

      Roberto Carlos Agis-Balboa, Dario Arcos-Diaz, Jessica Wittnam, Nambirajan Govindarajan, Kim Blom, Susanne Burkhardt, Ulla Haladyniak, Hope Yao Agbemenyah, Athanasios Zovoilis, Gabriella Salinas-Riester, Lennart Opitz, Farahnaz Sananbenesi and Andre Fischer

      Article first published online: 26 AUG 2011 | DOI: 10.1038/emboj.2011.293

      Contextual fear memory results in altered expression of Insulin-growth factor 2, IGF2, pathway components. Modulation of hippocampal IGF2 signalling affects the extinction of fear memories.

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      Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas (pages 4084–4097)

      Clare V LeFave, Massimo Squatrito, Sandra Vorlova, Gina L Rocco, Cameron W Brennan, Eric C Holland, Ying-Xian Pan and Luca Cartegni

      Article first published online: 13 SEP 2011 | DOI: 10.1038/emboj.2011.259

      This study reveals two alternative splicing events that contribute to the development of glioma. HnRNPH is shown to control production of a pro-survival splice variant of the death-domain adaptor protein IG20-MADD and the motility-enhancing isoform of the RON receptor tyrosine kinase.

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      A pH-regulated dimeric bouquet in the structure of von Willebrand factor (pages 4098–4111)

      Yan-Feng Zhou, Edward T Eng, Noritaka Nishida, Chafen Lu, Thomas Walz and Timothy A Springer

      Article first published online: 19 AUG 2011 | DOI: 10.1038/emboj.2011.297

      Hemostatic protein VWF promotes platelet binding to site of vascular injury. This study shows how VWF dimers ‘zip up’ at the C-terminal domains to form a bouquet-like structure, allowing packing into Weibel–Palade bodies and rapid release for secretion.

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