Abstract:
:The DNA-damage response (DDR) ensures genome stability and proper inheritance of genetic information, both of which are essential to survival. It is presently unclear to what extent other signaling pathways modulate DDR function. Here we show that Notch receptor binds and inactivates ATM kinase and that this mechanism is evolutionarily conserved in Caenorhabditis elegans, Xenopus laevis and humans. In C. elegans, the Notch pathway impairs DDR signaling in gonad germ cells. In mammalian cells, activation of human Notch1 leads to reduced ATM signaling in a manner independent of Notch1 transcriptional activity. Notch1 binds directly to the regulatory FATC domain of ATM and inhibits ATM kinase activity. Notch1 and ATM activation are inversely correlated in human breast cancers, and inactivation of ATM by Notch1 contributes to the survival of Notch1-driven leukemia cells upon DNA damage.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Vermezovic J,Adamowicz M,Santarpia L,Rustighi A,Forcato M,Lucano C,Massimiliano L,Costanzo V,Bicciato S,Del Sal G,d'Adda di Fagagna Fdoi
10.1038/nsmb.3013subject
Has Abstractpub_date
2015-05-01 00:00:00pages
417-24issue
5eissn
1545-9993issn
1545-9985pii
nsmb.3013journal_volume
22pub_type
杂志文章abstract::DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn(2+) comple...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2146
更新日期:2011-10-09 00:00:00
abstract::Mutually exclusive splicing is a regulated means to generate protein diversity, but the underlying mechanisms are poorly understood. Here comparative genome analysis revealed the built-in intronic elements for controlling mutually exclusive splicing of the 14-3-3ξ pre-mRNA. These elements are clade specific but are ev...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1959
更新日期:2011-02-01 00:00:00
abstract::Type I interferons (IFNs) are multifunctional cytokines that regulate immune responses and cellular functions but also can have detrimental effects on human health. A tight regulatory network therefore controls IFN signaling, which in turn may interfere with medical interventions. The JAK-STAT signaling pathway transm...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3378
更新日期:2017-03-01 00:00:00
abstract::No-go decay (NGD) targets mRNAs with stalls in translation elongation for endonucleolytic cleavage in a process involving the Dom34 and Hbs1 proteins. The crystal structure of a Schizosaccharomyces pombe Dom34-Hbs1 complex reveals an overall shape similar to that of eRF1-eRF3-GTP and EF-Tu-tRNA-GDPNP. Similarly to eRF...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1922
更新日期:2010-10-01 00:00:00
abstract::Although the two B-family human DNA polymerases, pol δ and pol ε, are responsible for the bulk of nuclear genome replication, at least 14 additional polymerases have roles in nuclear DNA repair and replication. In this issue, newly reported crystal structures of two specialized A-family polymerases, pol δ and pol ε, e...
journal_title:Nature structural & molecular biology
pub_type: 评论,杂志文章
doi:10.1038/nsmb.3006
更新日期:2015-04-01 00:00:00
abstract::Protein synthesis by the ribosome can fail for numerous reasons including faulty mRNA, insufficient availability of charged tRNAs and genetic errors. All organisms have evolved mechanisms to recognize stalled ribosomes and initiate pathways for recycling, quality control and stress signaling. Here we review the discov...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章,评审
doi:10.1038/nsmb.3147
更新日期:2016-01-01 00:00:00
abstract::Desensitization is a universal feature of ligand-gated ion channels. Using the crystal structure of the GluR2 L483Y mutant channel as a guide, we attempted to build non-desensitizing kainate-subtype glutamate receptors. Success was achieved for GluR5, GluR6 and GluR7 with intermolecular disulfide cross-links but not b...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1178
更新日期:2006-12-01 00:00:00
abstract::Maintenance of cell volume against osmotic change is crucial for proper cell functions. Leucine-rich repeat-containing 8 proteins are anion-selective channels that extrude anions to decrease the cell volume on cellular swelling. Here, we present the structure of human leucine-rich repeat-containing 8A, determined by s...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-018-0109-6
更新日期:2018-09-01 00:00:00
abstract::Interactions between Src homology 2 (SH2) domains and phosphotyrosine sites regulate tyrosine kinase signaling networks. Selective perturbation of these interactions is challenging due to the high homology among the 120 human SH2 domains. Using an improved phage-display selection system, we generated a small antibody ...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1793
更新日期:2010-04-01 00:00:00
abstract::Gating the ion-permeation pathway in K(+) channels requires conformational changes in activation and inactivation gates. Here we have investigated the structural alterations associated with pH-dependent inactivation gating of the KcsA-Kv1.3 K(+) channel using solid-state NMR spectroscopy in direct reference to electro...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.1430
更新日期:2008-06-01 00:00:00
abstract::Newly synthesized polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting, but the spatial and temporal coordination of these steps is unclear. We show that Escherichia coli methionine aminopeptidase (MAP) associates wi...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2615
更新日期:2013-07-01 00:00:00
abstract::Frizzled planar cell polarity (PCP) signaling regulates cell motility in several tissues, including ommatidial rotation in Drosophila melanogaster. The Nemo kinase (Nlk in vertebrates) has also been linked to cell-motility regulation and ommatidial rotation but its mechanistic role(s) during rotation remain obscure. W...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2049
更新日期:2011-06-01 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::Many viruses bypass canonical cap-dependent translation in host cells by using internal ribosomal entry sites (IRESs) in their transcripts; IRESs hijack initiation factors for the assembly of initiation complexes. However, it is currently unknown how IRES RNAs recognize initiation factors that have no endogenous RNA b...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3280
更新日期:2016-09-01 00:00:00
abstract::Thymic stromal lymphopoietin (TSLP), a cytokine produced by epithelial cells at barrier surfaces, is pivotal for the development of widespread chronic inflammatory disorders such as asthma and atopic dermatitis. The structure of the mouse TSLP-mediated signaling complex reveals how TSLP establishes extensive interface...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2794
更新日期:2014-04-01 00:00:00
abstract::In this article, the Ponceau staining presented in Fig. 1b (right, bottom) does not follow best practices for figure preparation since itinadvertently included duplications from the Ponceau staining presented in Supplementary Fig. 1b (for which the same preparation ofnucleosomes from HeLa cells had been used). A new F...
journal_title:Nature structural & molecular biology
pub_type: 已发布勘误
doi:10.1038/s41594-018-0090-0
更新日期:2018-08-01 00:00:00
abstract::Gene expression is inherently stochastic; precise gene regulation by transcription factors is important for cell-fate determination. Many transcription factors regulate their own expression, suggesting that autoregulation counters intrinsic stochasticity in gene expression. Using a new strategy, cotranslational activa...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2336
更新日期:2012-08-01 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::We have isolated a soluble cytochrome from Shewanella oneidensis that contains eight covalently attached heme groups and determined its crystal structure. One of these hemes exhibits novel ligation of the iron atom by the epsilon-amino group of a lysine residue, despite its attachment via a typical CXXCH motif. This h...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb827
更新日期:2004-10-01 00:00:00
abstract::Induced transcription through CAG repeats in human cells increases repeat contraction approximately 15-fold in both confluent and proliferating cells. Repeats are stabilized against contraction by siRNA knockdown of MSH2, MSH3 or XPA, but not by knockdown of MSH6, XPC or FEN1. These results define a pathway for CAG.CT...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1042
更新日期:2006-02-01 00:00:00
abstract::Bacteriophage T4 and related viruses have a contractile tail that serves as an efficient mechanical device for infecting bacteria. A three-dimensional cryo-EM reconstruction of the mature T4 tail assembly at 15-A resolution shows the hexagonal dome-shaped baseplate, the extended contractile sheath, the long tail fiber...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb975
更新日期:2005-09-01 00:00:00
abstract::Allosteric interactions are typically considered to proceed through a series of discrete changes in bonding interactions that alter the protein conformation. Here we show that allostery can be mediated exclusively by transmitted changes in protein motions. We have characterized the negatively cooperative binding of cA...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb1132
更新日期:2006-09-01 00:00:00
abstract::BAK and BAX are essential mediators of apoptosis that oligomerize in response to death cues, thereby causing permeabilization of the mitochondrial outer membrane. Their transition from quiescent monomers to pore-forming oligomers involves a well-characterized symmetric dimer intermediate. However, no essential seconda...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-020-0494-5
更新日期:2020-11-01 00:00:00
abstract::Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial receptor interaction has been difficult to study because of major CD4-induced structural rearrangements. Here we used cryog...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.3382
更新日期:2017-04-01 00:00:00
abstract::Bacterial transcription is controlled by sigma factors, the RNA polymerase subunits that act as initiation factors. Although a single housekeeping sigma factor enables transcription from thousands of promoters, environmentally induced sigma factors redirect gene expression toward small regulons to carry out focused re...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2777
更新日期:2014-03-01 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::Primary microRNA cleavage by the Drosha-Dgcr8 'Microprocessor' complex is critical for microRNA biogenesis. Yet, the Microprocessor may also cleave other nuclear RNAs in a nonspecific manner. We studied Microprocessor function using mathematical modeling and experiments in mouse and human tissues. We found that the au...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb.2293
更新日期:2012-05-13 00:00:00
abstract::Members of the X11/Mint family of multidomain adaptor proteins are composed of a divergent N terminus, a conserved PTB domain and a pair of C-terminal PDZ domains. Many proteins can interact with the PDZ tandem of X11 proteins, although the mechanism of such interactions is unclear. Here we show that the highly conser...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb958
更新日期:2005-08-01 00:00:00
abstract::The ClpAP complex is a conserved bacterial protease that unfolds and degrades proteins targeted for destruction. The ClpA double-ring hexamer powers substrate unfolding and translocation into the ClpP proteolytic chamber. Here, we determined high-resolution structures of wild-type Escherichia coli ClpAP undergoing act...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/s41594-020-0409-5
更新日期:2020-05-01 00:00:00
abstract::The ability of barrier-to-autointegration factor (BAF) to bind and bridge DNA in a sequence-independent manner is crucial for its role in retroviral integration and a variety of cellular processes. To better understand this behavior, we solved the crystal structure of BAF bound to DNA. The structure reveals that BAF b...
journal_title:Nature structural & molecular biology
pub_type: 杂志文章
doi:10.1038/nsmb989
更新日期:2005-10-01 00:00:00