Abstract：
:Natural chromosome ends resemble double-stranded DNA breaks, but they do not activate a damage response in healthy cells. Telomeres therefore have evolved to solve the 'end-protection problem' by inhibiting multiple DNA damage-response pathways. During the past decade, the view of telomeres has progressed from simple caps that hide chromosome ends to complex machineries that have an active role in organizing the genome. Here we focus on mammalian telomeres and summarize and interpret recent discoveries in detail, focusing on how repair pathways are inhibited, how resection and replication are controlled and how these mechanisms govern cell fate during senescence, crisis and transformation.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Arnoult N,Karlseder Jdoi
10.1038/nsmb.3092subject
Has Abstractpub_date
2015-11-01 00:00:00pages
859-66issue
11eissn
1545-9993issn
1545-9985pii
nsmb.3092journal_volume
22pub_type
杂志文章,评审abstract：:Many classes of small RNA (sRNA) involved in RNA silencing are generated by double-stranded RNA (dsRNA) processing. Although principles of sRNA biogenesis have emerged, newly identified classes of sRNAs have features that suggest additional biogenesis mechanisms. Tetrahymena thermophila expresses one such class, compr...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1262
更新日期：2007-07-01 00:00:00
abstract：:Core Factor (CF) is a conserved RNA polymerase (Pol) I general transcription factor comprising Rrn6, Rrn11 and the TFIIB-related subunit Rrn7. CF binds TATA-binding protein (TBP), Pol I and the regulatory factors Rrn3 and upstream activation factor. We used chemical cross-linking-MS to determine the molecular architec...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2873
更新日期：2014-09-01 00:00:00
abstract：:We developed an experimental system for studying genome instability caused by fragile X (CGG)n repeats in mammalian cells. Our method uses a selectable cassette carrying the HyTK gene under the control of the FMR1 promoter with (CGG)n repeats in its 5' UTR, which is integrated into the unique RL5 site in murine erythr...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-018-0094-9
更新日期：2018-08-01 00:00:00
abstract：:To our knowledge, no structural study to date has characterized, in an intact receptor, the coupling of conformational change in extracellular domains through a single-pass transmembrane domain to conformational change in cytoplasmic domains. Here we examine such coupling, and its unexpected complexity, using nearly f...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2092
更新日期：2011-08-07 00:00:00
abstract：:Clustered codons that pair to low-abundance tRNA isoacceptors can form slow-translating regions in the mRNA and cause transient ribosomal arrest. We report that folding efficiency of the Escherichia coli multidomain protein SufI can be severely perturbed by alterations in ribosome-mediated translational attenuation. S...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1554
更新日期：2009-03-01 00:00:00
abstract：:We developed a 'computational second-site suppressor' strategy to redesign specificity at a protein-protein interface and applied it to create new specifically interacting DNase-inhibitor protein pairs. We demonstrate that the designed switch in specificity holds in in vitro binding and functional assays. We also show...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb749
更新日期：2004-04-01 00:00:00
abstract：:Integral membrane proteins are generally believed to have unique membrane topologies. However, it has been suggested that dual-topology proteins that adopt a mixture of two opposite orientations in the membrane may exist. Here we show that the membrane orientations of five dual-topology candidates identified in Escher...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1057
更新日期：2006-02-01 00:00:00
abstract：:The tandem zinc finger (TZF) domain of the protein TIS11d binds to the class II AU-rich element (ARE) in the 3' untranslated region (3' UTR) of target mRNAs and promotes their deadenylation and degradation. The NMR structure of the TIS11d TZF domain bound to the RNA sequence 5'-UUAUUUAUU-3' comprises a pair of novel C...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb738
更新日期：2004-03-01 00:00:00
abstract：:We present a structural analysis of the folding transition states of three SH3 domains. Our results reveal that the secondary structure is not yet fully formed at this stage of folding and that the solvent is only partially excluded from the interior of the protein. Comparison of the members of the transition state en...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb765
更新日期：2004-05-01 00:00:00
abstract：:In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contain...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2629
更新日期：2013-08-01 00:00:00
abstract：:Mg-ADP release is considered to be a crucial process for the regulation and motility of kinesin. To gain insight into the structural basis of this process, we solved the atomic structures of kinesin superfamily protein-1A (KIF1A) during and after Mg(2+) release. On the basis of new structural and mutagenesis data, we ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1487
更新日期：2008-10-01 00:00:00
abstract：:Argonaute (Ago) proteins mediate silencing of nucleic acid targets by small RNAs. In fission yeast, Ago1, Tas3 and Chp1 assemble into a RITS complex, which silences transcription near centromeres. Here we describe a repetitive motif within Tas3, termed the 'Argonaute hook', that is conserved from yeast to humans and b...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1302
更新日期：2007-10-01 00:00:00
abstract：:Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment is maintained at sites ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3185
更新日期：2016-04-01 00:00:00
abstract：:Translation has a fundamental function in defining the fate of the transcribed genome. RNA-sequencing (RNA-seq) data enable the quantification of complex transcript mixtures, often detecting several transcript isoforms of unknown functions for one gene. Here, we describe ORFquant, a method to annotate and quantify tra...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-020-0450-4
更新日期：2020-08-01 00:00:00
abstract：:Although both homologous recombination (HR) and nonhomologous end joining can repair DNA double-strand breaks (DSBs), the mechanisms by which one of these pathways is chosen over the other remain unclear. Here we show that transcriptionally active chromatin is preferentially repaired by HR. Using chromatin immunopreci...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2796
更新日期：2014-04-01 00:00:00
abstract：:To determine which genomic features promote homologous recombination, we created a genome-wide map of gene targeting sites. We used an adeno-associated virus vector to target identical loci introduced as transcriptionally active retroviral vectors. A comparison of ~2,000 targeted and untargeted sites showed that targe...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2895
更新日期：2014-11-01 00:00:00
abstract：:The structure of the Sortilin ectodomain in complex with neurotensin has been determined at 2-A resolution, revealing that the C-terminal part of neurotensin binds in the tunnel of a ten-bladed beta-propeller domain. Binding competition studies suggest that additional binding sites, for example, for the prodomain of n...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1543
更新日期：2009-01-01 00:00:00
abstract：:MicroRNAs (miRNAs) interact with target sites located in the 3' untranslated regions (3' UTRs) of mRNAs to downregulate their expression when the appropriate miRNA is bound to target mRNA. To establish the functional importance of target-site localization in the 3' UTR, we modified the stop codon to extend the coding ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1552
更新日期：2009-02-01 00:00:00
abstract：:Advances in structure determination of the bacterial and eukaryotic transcription machinery have led to a marked increase in the understanding of the mechanism of transcription. Models for the specific assembly of the RNA polymerase II transcription machinery at a promoter, conformational changes that occur during ini...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章,评审
doi：10.1038/nsmb763
更新日期：2004-05-01 00:00:00
abstract：:Otopetrins (Otop1-Otop3) comprise one of two known eukaryotic proton-selective channel families. Otop1 is required for otoconia formation and a candidate mammalian sour taste receptor. Here we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs. The structures reveal a dimeric architectur...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-019-0235-9
更新日期：2019-06-01 00:00:00
abstract：:Jun dimerization protein-2 (JDP2) is a component of the AP-1 transcription factor that represses transactivation mediated by the Jun family of proteins. Here, we examine the functional mechanisms of JDP2 and show that it can inhibit p300-mediated acetylation of core histones in vitro and in vivo. Inhibition of histone...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1063
更新日期：2006-04-01 00:00:00
abstract：:Allosteric proteins transition among different conformational states in a ligand-dependent manner. Upon resolution of a protein's individual states, one can determine the probabilities of these states, thereby dissecting the energetic mechanisms underlying their conformational changes. Here we examine individual regul...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-019-0275-1
更新日期：2019-09-01 00:00:00
abstract：:Mycobacterium tuberculosis uses a proteasome system that is analogous to the eukaryotic ubiquitin-proteasome pathway and is required for pathogenesis. However, the bacterial analog of ubiquitin, prokaryotic ubiquitin-like protein (Pup), is an intrinsically disordered protein that bears little sequence or structural re...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1918
更新日期：2010-11-01 00:00:00
abstract：:The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase fam...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1705
更新日期：2010-01-01 00:00:00
abstract：:Bacterial tRNA adenosine deaminases (TadAs) catalyze the hydrolytic deamination of adenosine to inosine at the wobble position of tRNA(Arg2), a process that enables this single tRNA to recognize three different arginine codons in mRNA. In addition, inosine is also introduced at the wobble position of multiple eukaryot...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1047
更新日期：2006-02-01 00:00:00
abstract：:In eukaryotic cells, many introns are constitutively, rather than alternatively, spliced and therefore do not contribute to isoform diversification. It has remained unclear what functional roles such constitutive splicing provides. To explore this issue, we asked how splicing affects the efficiency with which individu...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-019-0226-x
更新日期：2019-06-01 00:00:00
abstract：:The computational design of α-helical membrane proteins is still in its infancy but has already made great progress. De novo design allows stable, specific and active minimal oligomeric systems to be obtained. Computational reengineering can improve the stability and function of naturally occurring membrane proteins. ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3231
更新日期：2016-06-07 00:00:00
abstract：:Microtubules are regulated by post-translational modifications of tubulin. The ligation and cleavage of the carboxy-terminal tyrosine of α-tubulin impact microtubule functions during mitosis, cardiomyocyte contraction and neuronal processes. Tubulin tyrosination and detyrosination are mediated by tubulin tyrosine liga...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-019-0242-x
更新日期：2019-07-01 00:00:00
abstract：:The PHD finger protein 1 (PHF1) is essential in epigenetic regulation and genome maintenance. Here we show that the Tudor domain of human PHF1 binds to histone H3 trimethylated at Lys36 (H3K36me3). We report a 1.9-Å resolution crystal structure of the Tudor domain in complex with H3K36me3 and describe the molecular me...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2435
更新日期：2012-12-01 00:00:00
abstract：:Seven-helix membrane proteins represent a challenge for structural biology. Here we report the first NMR structure determination of a detergent-solubilized seven-helix transmembrane (7TM) protein, the phototaxis receptor sensory rhodopsin II (pSRII) from Natronomonas pharaonis, as a proof of principle. The overall qua...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1807
更新日期：2010-06-01 00:00:00
