Nature Structural & Molecular Biology Contents: January 2012 Volume #19 pp 1 - 127

TABLE OF CONTENTS January 2012 Volume 19, Issue 1 News and Views Research Highlights Review Articles Brief Communication Technical Reports Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Instruct is now accepting proposals for access to the cutting-edge European structural biology technology. Submit your proposal here. The Instruct Hub also offers a calendar of events, jobs postings, forums, and lots of other useful information. Join our thriving community by becoming a member of the Instruct Hub today.   Advertisement Focus on Membrane dynamics The January 2012 issue of Nature Cell Biology presents a series of review articles by leading scientists on recent developments in membrane dynamics - including endocytosis, and vesicle biogenesis and transport - and the importance of these processes in development and disease. Access the Focus online: www.nature.com/ncb/webfocus/membranedynamics   News and Views Top Finding the missing links in EGFR pp1 - 3 Nicholas J Bessman and Mark A Lemmon doi:10.1038/nsmb.2221 Structural studies of the epidermal growth factor receptor (EGFR) have advanced greatly in recent years, but they have used a 'divide-and-conquer' approach for independent study of the intracellular and extracellular regions. Several recent papers provide important new perspectives on 'undivided' EGFR and describe the initial steps in reconstructing signaling behavior of the intact receptor. Full Text | PDF Claims and counterclaims of X-chromosome compensation pp3 - 5 James A Birchler doi:10.1038/nsmb.2218 Is there upregulation of the single active X chromosome in mammals or not? Recent studies take different points of view. Full Text | PDF See also: Article by Yildirim et al. Thresholds of replication stress signaling in cancer development and treatment pp5 - 7 Jiri Bartek, Martin Mistrik and Jirina Bartkova doi:10.1038/nsmb.2220 Oncogene-induced replication stress and DNA damage are among the hallmarks of cancer. A recent study explores how different levels of replication stress affect animal development and tumorigenesis, and how targeting of the replication stress-signaling pathway of ATR and Chk1 kinases can be exploited for selective killing of cancer cells. Full Text | PDF Research Highlights Methylating fingers | Structural basis of silencing | Stalled out | Rli1 does the splits Review New approaches for dissecting protease functions to improve probe development and drug discovery pp9 - 16 Edgar Deu, Martijn Verdoes and Matthew Bogyo doi:10.1038/nsmb.2203 Abstract | Full Text | PDF Structural & Molecular Biology JOBS of the week Study of stem cells by Fourier transform Infrared microspectroscopy (FTIR) Ministero dell'Istruzione, dell'Università e della Ricerca Study of stem cells by Fourier transform Infrared microspectroscopy (FTIR) Ministero dell'Istruzione, dell'Università e della Ricerca International PhD Programme Institute of Molecular Biology Assistant or Associate Professor Yale University More Science jobs from Structural & Molecular Biology EVENT Mutations, Malignancy and Memory - Antibodies and Immunity (C6) 18th - 22nd March 2012 MA, US More science events from Articles Top RAD51- and MRE11-dependent reassembly of uncoupled CMG helicase complex at collapsed replication forks pp17 - 24 Yoshitami Hashimoto, Fabio Puddu and Vincenzo Costanzo doi:10.1038/nsmb.2177 A system to reconstitute a collapsed replication fork using Xenopus laevis egg extracts is developed. The study shows that upon fork collapse, DNA Pol epsilon and the GINS complex are uncoupled from the replisome, and their reloading onto DNA requires repair proteins Rad51 and Mre11. Abstract | Full Text | PDF A unique H2A histone variant occupies the transcriptional start site of active genes pp25 - 30 Tatiana A Soboleva, Maxim Nekrasov, Anuj Pahwa, Rohan Williams, Gavin A Huttley and David J Tremethick doi:10.1038/nsmb.2161 The histone variant H2A.Bbd inhibits folding of nucleosomal arrays and reverses chromatin-mediated transcriptional repression in vitro. New studies have uncovered the related mouse H2A variant H2A.Lap1 as a novel component of the transcription start site of active genes during specific stages of spermatogenesis, which enables transcriptional activation by unfolding the chromatin locally. Abstract | Full Text | PDF Signal-dependent dynamics of transcription factor translocation controls gene expression pp31 - 39 Nan Hao and Erin K O'Shea doi:10.1038/nsmb.2192 The Msn2 transcription factor is translocated to the nucleus to activate transcription of hundreds of genes in response to various environmental stimuli. Experimental and computational single-molecule analyses reveal how different stimuli elicit different dynamical patterns of Msn2 translocation, which are interpreted by promoters with distinct properties to produce specific patterns of target gene expression. Abstract | Full Text | PDF Intrinsic tethering activity of endosomal Rab proteins pp40 - 47 Sheng-Ying Lo, Christopher L Brett, Rachael L Plemel, Marissa Vignali, Stanley Fields, Tamir Gonen and Alexey J Merz doi:10.1038/nsmb.2162 Rab small G proteins regulate membrane trafficking events by recruiting effectors that mediate vesicle tethering. In vitro studies now suggest that Vps21 and other endosomal Rabs in budding yeast can undergo GTP-regulated Rab-Rab interactions that drive tethering in the absence of effectors, implying that they have an intrinsic tethering activity that may function in concert with conventional effectors. Abstract | Full Text | PDF Ndc10 is a platform for inner kinetochore assembly in budding yeast pp48 - 55 Uhn-Soo Cho and Stephen C Harrison doi:10.1038/nsmb.2178 Kinetochores assemble on centromeric DNA and link centromeres to spindle microtubules, thus allowing proper segregation during mitosis. The kinetochore subunit Ndc10 makes contacts with centromeric DNA elements, which are now directly observed in a crystal structure. Along with biochemical analyses, the work indicates that Ndc10 functions as a central organizing hub to assemble the inner kinetochore. Abstract | Full Text | PDF X-chromosome hyperactivation in mammals via nonlinear relationships between chromatin states and transcription pp56 - 61 Eda Yildirim, Ruslan I Sadreyev, Stefan F Pinter and Jeannie T Lee doi:10.1038/nsmb.2195 In addition to balancing X-chromosome dosage between males and females via X inactivation, mammals also balance dosage of X chromosomes and autosomes. Allele-specific chromatin immunoprecipitation with deep sequencing (ChIP-seq) analyses now show that the active X chromosome is upregulated at the level of both transcription initiation and elongation. Abstract | Full Text | PDF See also: News and Views by Birchler An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains pp62 - 71 Julien D F Licchesi, Juliusz Mieszczanek, Tycho E T Mevissen, Trevor J Rutherford, Masato Akutsu, Satpal Virdee, Farid El Oualid, Jason W Chin, Huib Ovaa, Mariann Bienz and David Komander doi:10.1038/nsmb.2169 The OTU domain deubiquitinase TRABID specifically hydrolyzes atypical Lys29- and Lys33-linked diubiquitin chains. Structural analysis of TRABID reveals an unpredicted ankyrin-repeat domain that binds ubiquitin and is crucial for TRABID efficiency and linkage specificity in vitro and in vivo. Abstract | Full Text | PDF Mechanism of mismatch recognition revealed by human MutSß bound to unpaired DNA loops pp72 - 78 Shikha Gupta, Martin Gellert and Wei Yang doi:10.1038/nsmb.2175 Eukaryotic MutSß is a heterodimer composed of Msh2 and Msh3 that recognizes insertion-deletion loops (IDLs) and 3′ overhangs during mismatch repair. Now crystal structures of MutSß in complex with DNA, containing IDLs of varying lengths, reveal that this complex interacts with its substrate differently than MutSa and bacterial MutS do. Abstract | Full Text | PDF The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-β1−40 peptide pp79 - 83 Priyanka Narayan, Angel Orte, Richard W Clarke, Benedetta Bolognesi, Sharon Hook, Kristina A Ganzinger, Sarah Meehan, Mark R Wilson, Christopher M Dobson and David Klenerman doi:10.1038/nsmb.2191 Genome-wide association studies have established a link between the extracellular chaperone clusterin and susceptibility to Alzheimer's disease. A fluorescence approach is now used to reveal that clusterin sequesters Aβ1–40 oligomers and prevents them from undergoing further aggregation. Abstract | Full Text | PDF Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of pluripotency factor Lin28  pp84 - 89 Fionna E Loughlin, Luca F R Gebert, Harry Towbin, Andreas Brunschweiger, Jonathan Hall and Frédéric H-T Allain doi:10.1038/nsmb.2202 Lin28 prevents the processing of pre-let-7 RNAs, but it is not clear where the Lin28 RNA binding domains interact with the RNA. The NMR structure of the Lin28 zinc knuckles with a short RNA motif reveals that each knuckle interacts with an AG dinucleotide, allowing the determination of a consensus motif for pre-let-7 recognition. Abstract | Full Text | PDF Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi pp90 - 97 Caroline Thivierge, Neetha Makil, Mathieu Flamand, Jessica J Vasale, Craig C Mello, James Wohlschlegel, Darryl Conte Jr and Thomas F Duchaine doi:10.1038/nsmb.2186 The type III ribonuclease DCR-1 is essential for ERI endogenous RNAi and exogenous RNAi in Caenorhabditis elegans. A new study shows that DCR-1 forms exclusive complexes in each pathway, and characterization of the ERI complex implicates a tudor domain protein in tethering an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi. Abstract | Full Text | PDF Mispaired rNMPs in DNA are mutagenic and are targets of mismatch repair and RNases H pp98 - 104 Ying Shen, Kyung Duk Koh, Bernard Weiss and Francesca Storici doi:10.1038/nsmb.2176 Ribonucleoside monophosphates (rNMPs) are often incorporated into genomic DNA. Misincorporated rNMPs are now shown to be repaired by mismatch repair and RNases H. If not repaired, they can serve as a template for DNA synthesis and can cause mutagenesis in Escherichia coli and yeast. Abstract | Full Text | PDF Brief Communication Top Single-molecule studies reveal the function of a third polymerase in the replisome pp113 - 116 Roxana E Georgescu, Isabel Kurth and Mike E O'Donnell doi:10.1038/nsmb.2179 Recent work has indicated that the Escherichia coli replisome contains three DNA polymerases that are used to replicate two parental strands. A single-molecule approach is now used to compare replisomes reconstituted with two or three polymerases, revealing that the presence of a third polymerase ensures higher processivity overall and more efficient replication of the lagging strand. First paragraph | Full Text | PDF Technical Reports Top Fluorescent fusion protein knockout mediated by anti-GFP nanobody pp117 - 121 Emmanuel Caussinus, Oguz Kanca and Markus Affolter doi:10.1038/nsmb.2180 The combination of an F-box domain with a single-domain antibody that recognizes green fluorescent protein (GFP) now allows controlled depletion of GFP fusions in mammalian cells and in flies. This system, called deGradFP, should be widely useful, as GFP fusions are available for many proteins in model organisms. Abstract | Full Text | PDF A metal switch for controlling the activity of molecular motor proteins pp122 - 127 Jared C Cochran, Yu Cheng Zhao, Dean E Wilcox and F Jon Kull doi:10.1038/nsmb.2190 NTPases use a metal ion, typically Mg2+, coordinated by a conserved serine or threonine residue, to enable phosphate binding and catalysis. Now cysteine substitutions at the switch 1 motif of different kinesins render them able to use Mn2+ instead of Mg2+, allowing their enzymatic and motor activities to be modulated by the ratio of Mg2+ to Mn2+. Abstract | Full Text | PDF Top Advertisement Nature.com presents Antibodypedia Finding the right antibody for the right application just got easier! Visit www.antibodypedia.com to find antibodies that have proved themselves effective for particular applications or to submit antibody validation data from your own experiments.   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. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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