Nature Structural & Molecular Biology Contents: November 2012 Volume #19 pp 1059 - 1201

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Subscribe   Facebook   RSS   Recommend to library   Twitter   News and Views Top The spindle-assembly checkpoint and the beauty of self-destruction   pp1059 - 1061 Andrea Musacchio and Andrea Ciliberto doi:10.1038/nsmb.2429 Mitotic exit follows shortly after microtubule attachment of the last unattached kinetochore. Two new studies illustrate the molecular basis of this dependency. See also: Article by Uzunova et al. New functions for DNA modifications by TET-JBP   pp1061 - 1064 Yun Huang and Anjana Rao doi:10.1038/nsmb.2437 TET and JBP proteins catalyze the oxidation of methylated C bases in the mammalian genome and of the methyl group of T bases in kinetoplastid genomes, respectively. A recent study in Nature Structural & Molecular Biology suggests a new function of 5-methylcytosine oxidation in regulating RNA polymerase II elongation rate that is reminiscent of that of base J in transcription termination in Leishmania. Asymmetrically modified nucleosomes expand the histone code   pp1064 - 1066 Barth van Rossum, Wolfgang Fischle and Philipp Selenko doi:10.1038/nsmb.2433 According to the 'classical' view, histone modifications are established in an identical fashion on both copies of each of the four core histones, resulting in 'symmetrically' modified nucleosomes. Now, a new study challenges this notion by demonstrating that asymmetric histone modifications exist on individual mononucleosomes in native chromatin and that symmetric and asymmetric modifications signal different biological outcomes, suggesting a radically expanded histone code. Research Highlights Zucchini has bite | Pause-itively engaged | A PrePPI way to make predictions Review Cis-acting noncoding RNAs: friends and foes   pp1068 - 1075 Sonia Guil and Manel Esteller doi:10.1038/nsmb.2428 The number and types of known functional noncoding RNAs (ncRNAs) has increased considerably over the past few years, and both cis- and trans-acting ncRNAs have been reported. This Review focuses on long- and short-sized ncRNAs that act in cis; that is, where both the regulatory RNA and the target gene are transcribed from the same locus. Structural & Molecular Biology JOBS of the week PhD fellowships in Ultrafast Science and Structural Dynamics International Max Planck Research School for Ultrafast Imaging & Structural Dynamics (IMPRS-UFAST) Postdoctoral Position In Genomic Structural Variation: Endogenous Retroviruses Mary Poss, DVM, PhD Postdoctoral Associates Biochemistry / Structural Cell & Molecular Biology University at Albany Assistant Professor of Structural Biology / Biophysics ETH Postdoctoral Fellow, Structural Biology in DNA Damage Response The University of Hong Kong Li Ka Shing Faculty of Medicine More Science jobs from Structural & Molecular Biology EVENT 10th International Conference on Damage Assessment of Structures (DAMAS 2013) 08.-10.07.13 Dublin, Ireland More science events from Articles Top Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics   pp1076 - 1083 Maxim Nekrasov, Jana Amrichova, Brian J Parker, Tatiana A Soboleva, Cameron Jack, Rohan Williams, Gavin A Huttley and David J Tremethick doi:10.1038/nsmb.2424 Histone H2A.Z-containing nucleosomes flank the transcription start sites (TSSs) of active mammalian genes. A new study reveals that histone H2A.Z at the TSS is reduced during S phase, which coincides with its gain at centromeric and subtelomeric regions during M phase and mirrors an expansion of the nucleosome-depleted region, which, surprisingly, is unrelated to transcriptional activity. DVC1 (C1orf124) is a DNA damage–targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks   pp1084 - 1092 Anna Mosbech, Ian Gibbs-Seymour, Konstantinos Kagias, Tina Thorslund, Petra Beli, Lou Povlsen, Sofie Vincents Nielsen, Stine Smedegaard, Garry Sedgwick, Claudia Lukas, Rasmus Hartmann-Petersen, Jiri Lukas, Chunaram Choudhary, Roger Pocock, Simon Bekker-Jensen and Niels Mailand doi:10.1038/nsmb.2395 The AAA ATPase p97 (VCP) is thought to remove specific proteins from chromatin at sites of DNA damage, to allow proper repair or processing, but how p97 targets those sites was unclear. The protein DVC1 is now shown to localize to sites of replication stress and UV-light damage, and to be required for p97 recruitment. DVC1's localization to DNA damage sites requires its UBZ domain and PCNA-interacting motif but not PCNA ubiquitination. DVC1 deficiency caused retention of error-prone translesion polymerase η at foci after UV-light damage and increased mutagenesis levels. DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage   pp1093 - 1100 Emily J Davis, Christophe Lachaud, Paul Appleton, Thomas J Macartney, Inke Näthke and John Rouse doi:10.1038/nsmb.2394 The AAA ATPase p97 (VCP) is thought to remove specific proteins from chromatin at sites of DNA damage, to allow proper repair or processing, but how p97 targets those sites was unclear. The protein DVC1 is now shown to localize to sites of replication stress and UV-light damage, and to be required for p97 recruitment. DVC1's localization to DNA damage sites requires its UBZ domain and PCNA-interacting motif but not PCNA ubiquitination. DVC1 deficiency caused retention of error-prone translesion polymerase η at foci after UV-light damage and increased mutagenesis levels. Crystal structure of human CDC7 kinase in complex with its activator DBF4    pp1101 - 1107 Siobhan Hughes, Frédéric Elustondo, Andrea Di Fonzo, Frédéric G Leroux, Ai C Wong, Ambrosius P Snijders, Stephen J Matthews and Peter Cherepanov doi:10.1038/nsmb.2404 The kinase CDC7 is essential for replication initiation in eukaryote organisms. To exert its function, CDC7 requires its activator, DBF4. Now the crystal structures of a minimal CDC7–DBF4 complex, with bound nucleotide or inhibitor, along with functional analyses reveal that DBF4 wraps around CDC7, stabilizing the aC helix in the N lobe and tethering the C lobe of the kinase. Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II   pp1108 - 1115 Stéphane Larochelle, Ramon Amat, Kira Glover-Cutter, Miriam Sansó, Chao Zhang, Jasmina J Allen, Kevan M Shokat, David L Bentley and Robert P Fisher doi:10.1038/nsmb.2399 RNA polymerase II (pol II) frequently pauses in the promoter-proximal region to ensure gene-specific regulation and RNA quality control. New research demonstrates that the cyclin-dependent kinase Cdk7 can act to establish the promoter-proximal pause, through its control of the TFIIE-DSIF switch, and to release Pol II from the pause, through its ability to activate Cdk9. APC15 mediates CDC20 autoubiquitylation by APC/CMCC and disassembly of the mitotic checkpoint complex   pp1116 - 1123 Kristina Uzunova, Billy T Dye, Hannelore Schutz, Rene Ladurner, Georg Petzold, Yusuke Toyoda, Marc A Jarvis, Nicholas G Brown, Ina Poser, Maria Novatchkova, Karl Mechtler, Anthony A Hyman, Holger Stark, Brenda A Schulman and Jan-Michael Peters doi:10.1038/nsmb.2412 Activation of the anaphase-promoting complex/cyclosome (APC/C) depends on disassembly of the mitotic checkpoint complex (MCC), which has been proposed to require CDC20 autoubiquitylation. A new study involving reconstituted recombinant human APC/C supports the view that the APC15 subunit of APC/C localizes near the MCC binding site and mediates CDC20 autoubiquitylation, thereby promoting MCC disassembly. See also: News and Views by Musacchio & Ciliberto CLIP-seq of eIF4AIII reveals transcriptome-wide mapping of the human exon junction complex   pp1124 - 1131 Jérôme Saulière, Valentine Murigneux, Zhen Wang, Emélie Marquenet, Isabelle Barbosa, Olivier  Le Tonquèze, Yann Audic, Luc Paillard, Hugues Roest Crollius and Hervé Le Hir doi:10.1038/nsmb.2420 The exon junction complex (EJC) has a crucial role in various post-transcriptional control mechanisms. CLIP-Seq analysis of the human EJC component eIF4AIII has revealed peaks in canonical EJC-binding regions, including ~24 nucleotides upstream of exon junctions. Surprisingly, EJCs are also present elsewhere in the transcriptome, uncovering an unexpected heterogeneity of EJC association with mRNAs. LpxI structures reveal how a lipid A precursor is synthesized   pp1132 - 1138 Louis E Metzger IV, John K Lee, Janet S Finer-Moore, Christian R H Raetz and Robert M Stroud doi:10.1038/nsmb.2393 In Gram-negative bacterial outer membranes, lipid A serves as the anchor for lipopolysaccharide. Structural and biochemical data reveal that LpxI, an enzyme involved in lipid A synthesis, uses a hinge-like mechanism to deposit its product into the membrane through the binding of fresh substrate. Splicing switch of an epigenetic regulator by RNA helicases promotes tumor-cell invasiveness   pp1139 - 1146 Etienne Dardenne, Sandra Pierredon, Keltouma Driouch, Lise Gratadou, Magali Lacroix-Triki, Micaela Polay Espinoza, Eleonora Zonta, Sophie Germann, Hussein Mortada, Jean-Philippe Villemin, Martin Dutertre, Rosette Lidereau, Stéphan Vagner and Didier Auboeuf doi:10.1038/nsmb.2390 Both epigenetic and splicing regulation contribute to tumor progression, but how these contributions are linked is not well understood. A new study reveals a cascade of altered gene-expression events that underlie tumor progression, wherein splicing factors Ddx5 and Ddx17 control the alternative splicing of an epigenetic factor, macroH2A1, leading to transcriptional alterations that switch tumor cells to an invasive phenotype. Structure of a topoisomerase II–DNA–nucleotide complex reveals a new control mechanism for ATPase activity   pp1147 - 1154 Bryan H Schmidt, Neil Osheroff and James M Berger doi:10.1038/nsmb.2388 Type IIA topoisomerases (topos) control supercoiling and disentangle chromosomes by an ATP-dependent strand-passage mechanism. The structure of a full-length budding-yeast topo II in complex with DNA and an ATP analog now provides a picture of its architecture, revealing a structural basis for unidirectional strand passage and a DNA-induced control mechanism for ATP hydrolysis and topo activity. Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation   pp1155 - 1160 Scott B Rothbart, Krzysztof Krajewski, Nataliya Nady, Wolfram Tempel, Sheng Xue, Aimee I Badeaux, Dalia Barsyte-Lovejoy, Jorge Y Martinez, Mark T Bedford, Stephen M Fuchs, Cheryl H Arrowsmith and Brian D Strahl doi:10.1038/nsmb.2391 The E3 ubiquitin ligase UHRF1 has been genetically linked to the establishment and maintenance of DNA methylation in mammals. A new study now provides mechanistic insight by demonstrating that binding of UHRF1 to methylated histone H3 lysine 9 during mitosis is needed for stability of DNA methyltransferase 1 and the faithful propagation of DNA methylation. Multimodal microtubule binding by the Ndc80 kinetochore complex   pp1161 - 1167 Gregory M Alushin, Vivek Musinipally, Daniel Matson, John Tooley, P Todd Stukenberg and Eva Nogales doi:10.1038/nsmb.2411 Microtubules bind to the kinetochore at the Ndc80 complex, and this interaction is regulated by phosphorylation events at the N-terminal tail of Ndc80, mediated by the Aurora B kinase. The distinct functions of Ndc80 N-terminal tail are now dissected, revealing a region that binds tubulin and another that contacts the globular head of Ndc80. Both contacts are disrupted by phosphorylation, and the results lead to a mechanistic model for how phosphorylation of Ndc80 controls its interactions with microtubules. DICER- and AGO3-dependent generation of retinoic acid–induced DR2 Alu RNAs regulates human stem cell proliferation   pp1168 - 1175 QiDong Hu, Bogdan Tanasa, Michele Trabucchi, Wenbo Li, Jie Zhang, Kenneth A Ohgi, David W Rose, Christopher K Glass and Michael G Rosenfeld doi:10.1038/nsmb.2400 The biological importance of large numbers of retrotransposon-derived Alu repeats present in the human genome has been mysterious. New research reveals that many Alu repeats are bound and induced by retinoic acid receptor to generate RNA polymerase III–dependent transcripts, which are processed in a Dicer-dependent manner. The resulting short, so-called riRNAs post-transcriptionally downregulate target mRNAs, thereby modulating stem-cell proliferation. Crystal structure of adenovirus E3-19K bound to HLA-A2 reveals mechanism for immunomodulation   pp1176 - 1181 Lenong Li, Yasameen Muzahim and Marlene Bouvier doi:10.1038/nsmb.2396 Adenovirus infection can suppress antigen presentation by MHC I, by the action of transmembrane protein E3-19K, whose N-terminal domain localizes to the ER lumen and binds MHC I luminal domain. Now the crystal structure of E3-19K in complex with MHC I molecule HLA-A2 is presented, providing atomic-level insight into this interaction. Brief Communication Top Structural insights into ligand binding and gene expression control by an adenosylcobalamin riboswitch   pp1182 - 1184 Alla Peselis and Alexander Serganov doi:10.1038/nsmb.2405 Adenosylcobalamin is a form of vitamin B12 that serves as a coenzyme in different reactions and as a ligand for riboswitches to control bacterial gene expression. The crystal structure of a B12 riboswitch from Symbiobacterium thermophilum bound to its ligand adenosylcobalamin is now presented, revealing the determinants for ligand recognition and gene expression control. Resource Top Genome-wide nucleosome positioning during embryonic stem cell development   pp1185 - 1192 Vladimir B Teif, Yevhen Vainshtein, Maïwen Caudron-Herger, Jan-Philipp Mallm, Caroline Marth, Thomas Höfer and Karsten Rippe doi:10.1038/nsmb.2419 Tissue- and disease-specific features of nucleosome positioning have recently been reported. A new study set out to identify features of nucleosome positioning at functional genomic elements during lineage commitment from mouse embryonic stem cells to neural progenitors and embryonic fibroblasts. The results reveal regulatory mechanisms of cell differentiation that involve nucleosome positioning. Technical Report Top Convergent transcription induces transcriptional gene silencing in fission yeast and mammalian cells   pp1193 - 1201 Monika Gullerova and Nick J Proudfoot doi:10.1038/nsmb.2392 Previous studies have shown the potential for convergent transcription as a way to induce gene silencing. This Technical Report now demonstrates that introducing convergent transcription plasmids into either fission yeast or mammalian cells can be used to mediate long-term transcriptional gene silencing of endogenous genes, with major advantages over other gene silencing strategies. Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. 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