TABLE OF CONTENTS
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March 2015 Volume 22, Issue 3 |
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Epigenome Roadmap
Nature Publishing Group presents an online portal - the Epigenome Roadmap - which collects key research papers from The NIH Roadmap Epigenomics Program, complemented by thematical 'threads' to help the readers mine the wealth of available information.
Access the Epigenome Roadmap for FREE at: nature.com/epigenomeroadmap
Produced with exclusive support from Illumina |  | |
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Editorial | Top |
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Announcement: double-blind peer review p175 doi:10.1038/nsmb.2983 Nature and Nature Research Journals start offering anonymity to authors during the peer-review process. |
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News and Views | Top |
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 Ribonucleotides in DNA: hidden in plain sight pp176 - 178 Sue Jinks-Robertson and Hannah L Klein doi:10.1038/nsmb.2981 Mapping of ribonucleotides to single-nucleotide resolution in yeast genomes provides new insight into the enzymology of DNA replication.
See also: Article by Clausen et al. | Article by Daigaku et al. |  |  |  | Subversive bacteria reveal new tricks in their cytoskeleton-hijacking arsenal pp178 - 179 Roberto Dominguez doi:10.1038/nsmb.2976 During infection, pathogenic Yersinia species secrete the antiphagocytic factor YopO (or YpkA), which contains a kinase domain and a Rho GTPase guanine nucleotide-dissociation inhibitor (GDI) domain. The structure of YopO in complex with actin, along with biochemical analyses, reveals the mechanism by which YopO uses actin to activate its kinase domain and recruit, phosphorylate and deactivate actin-assembly factors implicated in phagocytic clearance of the bacterium.
See also: Article by Lee et al. |  |  |  | Secondary nucleation wears the BRICHOS in this family pp180 - 181 Frank A Ferrone doi:10.1038/nsmb.2980 A chaperone segment provides powerful evidence for the molecular mechanism underlying Alzheimer's disease.
See also: Article by Cohen et al. |  |  |  | The proteasome gets a grip on protein complexity pp181 - 183 Matthew A Humbard and Michael R Maurizi doi:10.1038/nsmb.2977 Amyloids escape elimination by the proteasome, and their accumulation and subsequent aggregation contribute to various neurodegenerative conditions. A signature feature of amyloidogenic proteins is extended sequences rich in single amino acids. In this issue, Matouschek and colleagues now show that, to initiate degradation, the proteasome prefers substrates that have disordered regions with complex amino acid composition, thus indicating why it fails to rid the cell of most amyloids.
See also: Article by Fishbain et al. |  | |  | |
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Research Highlights | Top |
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Released from the chains of death | m6A drives structural changes in RNA | TSPO through the crystal looking glass |
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Articles | Top |
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Tracking replication enzymology in vivo by genome-wide mapping of ribonucleotide incorporation pp185 - 191 Anders R Clausen, Scott A Lujan, Adam B Burkholder, Clinton D Orebaugh, Jessica S Williams et al. doi:10.1038/nsmb.2957 HydEn-seq, a new sequencing method that maps the distribution of ribonucleotides misincorporated by low-fidelity DNA polymerases in budding yeast, reveals unexpected strand-specific replication patterns in both nuclear and mitochondrial genomes.
See also: News and Views by Jinks-Robertson & Klein |
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A global profile of replicative polymerase usage pp192 - 198 Yasukazu Daigaku, Andrea Keszthelyi, Carolin A Müller, Izumi Miyabe, Tony Brooks et al. doi:10.1038/nsmb.2962 Genome-wide DNA polymerase usage maps determined in fission yeast, using a new sequencing strategy based on ribonucleotide misincorporation, track the division of labor between replicative polymerases and reveal locations and efficiencies of replication origins.
See also: News and Views by Jinks-Robertson & Klein |
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Structural basis for amyloidogenic peptide recognition by sorLA pp199 - 206 Yu Kitago, Masamichi Nagae, Zenzaburo Nakata, Maho Yagi-Utsumi, Shizuka Takagi-Niidome et al. doi:10.1038/nsmb.2954 The neuronal sorting receptor SorLA protects against Alzheimer's disease by binding Aβ peptides. Three new structures of the Vps10p Aβ-binding domain in ligand-free and ligand-bound forms explain the basis of SorLA peptide recognition. |
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A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers pp207 - 213 Samuel I A Cohen, Paolo Arosio, Jenny Presto, Firoz Roshan Kurudenkandy, Henrik Biverstål et al. doi:10.1038/nsmb.2971 Aβ peptide aggregation is associated with Alzheimer's disease, and Aβ fibrils can catalyze formation of toxic oligomers. Molecular chaperone Brichos binds to the fibril surface, inhibiting the catalytic cycle in vitro, and limits Aβ toxicity.
See also: News and Views by Ferrone |
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Sequence composition of disordered regions fine-tunes protein half-life pp214 - 221 Susan Fishbain, Tomonao Inobe, Eitan Israeli, Sreenivas Chavali, Houqing Yu et al. doi:10.1038/nsmb.2958 The proteasome initiates protein degradation at disordered regions within substrates. The proteasomal sequence preferences for the amino acid composition of these regions identified here affect protein half-life and explain unusual stability trends.
See also: News and Views by Humbard & Maurizi |
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Structures of CYLD USP with Met1- or Lys63-linked diubiquitin reveal mechanisms for dual specificity pp222 - 229 Yusuke Sato, Eiji Goto, Yuri Shibata, Yuji Kubota, Atsushi Yamagata et al. doi:10.1038/nsmb.2970 Tumor-suppressor protein CYLD cleaves linear and Lys63-linked ubiquitin chains. Structures of CYLD USP domain with Met1- and Lys63-linked diubiquitins and biochemical analyses reveal the mechanism for dual specificity and provide insight into tumor-associated mutations. |
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Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase θ pp230 - 237 Tatiana Kent, Gurushankar Chandramouly, Shane Michael McDevitt, Ahmet Y Ozdemir and Richard T Pomerantz doi:10.1038/nsmb.2961 Human DNA Polθ can mediate microhomology-mediated end-joining (MMEJ) of DNA molecules in cells and in vitro. Biochemistry work shows that Polθ promotes formation of DNA synapses and strand annealing, activities that require insertion loop 2. |
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Crystal structure of a phosphorylation-coupled vitamin C transporter pp238 - 241 Ping Luo, Xinzhe Yu, Weiguang Wang, Shilong Fan, Xiaochun Li et al. doi:10.1038/nsmb.2975 Crystal structures of the bacterial vitamin C transporter UlaA, a member of the AG family of the phosphoenolpyruvate-dependent phosphotransferase system, provide insights on binding to ascorbate and its transport across the cell membrane. |
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DNA interstrand cross-link repair requires replication-fork convergence pp242 - 247 Jieqiong Zhang, James M Dewar, Magda Budzowska, Anna Motnenko, Martin A Cohn et al. doi:10.1038/nsmb.2956 New biochemical analyses in Xenopus cell-free extracts show that two replication forks must converge on a DNA interstrand cross-link (ICL) to permit translesion synthesis and repair. |
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Yersinia effector YopO uses actin as bait to phosphorylate proteins that regulate actin polymerization pp248 - 255 Wei Lin Lee, Jonathan M Grimes and Robert C Robinson doi:10.1038/nsmb.2964 The crystal structure of Yersinia enterocolitica kinase YopO in complex with monomeric actin, together with biochemical analyses, reveals that YopO uses actin as bait to disrupt host cytoskeleton function and prevent phagocytosis.
See also: News and Views by Dominguez |
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Exon-intron circular RNAs regulate transcription in the nucleus pp256 - 264 Zhaoyong Li, Chuan Huang, Chun Bao, Liang Chen, Mei Lin et al. doi:10.1038/nsmb.2959 The identification of a new subclass of circular RNAs that are predominantly nuclear and promote transcription of their parental genes reveals a new regulatory function for these noncoding RNAs. |
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Brief Communications | Top |
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Structural basis for bifunctional peptide recognition at human δ-opioid receptor pp265 - 268 Gustavo Fenalti, Nadia A Zatsepin, Cecilia Betti, Patrick Giguere, Gye Won Han et al. doi:10.1038/nsmb.2965 Serial femtosecond crystallography of the human δ-opioid receptor in complex with an endomorphin-derived peptide reveals interactions that are important for understanding the pharmacology of opioid peptides and developing analgesics with reduced side effects. |
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Structure of a Yeast 40S–eIF1–eIF1A–eIF3–eIF3j initiation complex pp269 - 271 Christopher H S Aylett, Daniel Boehringer, Jan P Erzberger, Tanja Schaefer and Nenad Ban doi:10.1038/nsmb.2963 A high-resolution cryo-EM structure of yeast eIF3-bound 40S ribosomal subunits reveals the network of interactions between eIF3 subunits. |
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Corrigenda | Top |
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Corrigendum: Structure of EF-G-ribosome complex in a pretranslocation state p272 Yun Chen, Shu Feng, Veerendra Kumar, Rya Ero and Yong-Gui Gao doi:10.1038/nsmb0315-272a |
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Corrigendum: Cross-talking noncoding RNAs contribute to cell-specific neurodegeneration in SCA7 p272 Jennifer Y Tan, Keith W Vance, Miguel A Varela, Tamara Sirey, Lauren M Watson et al. doi:10.1038/nsmb0315-272b |
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Nature Insight Frontiers in biology
This year's Frontiers in Biology Insight covers the amygdala and how technology is helping us to understand its complex connectivity, innate lymphoid cells, nutrient-sensing mechanisms in mammals, a form of cell death called necroptosis, and the regulation and function of DNA methylation and its use as a cellular marker.
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