Abstract：
:Although DNA replication is a fundamental aspect of biology, it is not known what determines where DNA replication starts and stops in the human genome. We directly identified and quantitatively compared sites of replication initiation and termination in untransformed human cells. We found that replication preferentially initiates at the transcription start site of genes occupied by high levels of RNA polymerase II, and terminates at their polyadenylation sites, thereby ensuring global co-directionality of transcription and replication, particularly at gene 5' ends. During replication stress, replication initiation is stimulated downstream of genes and termination is redistributed to gene bodies; this globally reorients replication relative to transcription around gene 3' ends. These data suggest that replication initiation and termination are coupled to transcription in human cells, and propose a model for the impact of replication stress on genome integrity.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Chen YH,Keegan S,Kahli M,Tonzi P,Fenyö D,Huang TT,Smith DJdoi
10.1038/s41594-018-0171-0subject
Has Abstractpub_date
2019-01-01 00:00:00pages
67-77issue
1eissn
1545-9993issn
1545-9985pii
10.1038/s41594-018-0171-0journal_volume
26pub_type
杂志文章abstract：:Here we report the crystal structures of I.C and I.A wobble base pairs in the context of the ribosomal decoding center, clearly showing that the I.A base pair is of an I(anti).A(anti) conformation, as predicted by Crick. Additionally, the structures enable the observation of changes in the anticodon to allow purine-pu...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb866
更新日期：2004-12-01 00:00:00
abstract：:The highly contagious measles virus infects millions of individuals worldwide, causing serious disease in children of developing countries. Infection is initiated by attachment of the measles virus hemagglutinin (MV-H), a glycoprotein anchored to the virus envelope, to the host cell receptors CD46 or signaling lymphoc...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1726
更新日期：2010-01-01 00:00:00
abstract：:The RNA polymerase II (RNAPII) C-terminal domain (CTD) heptapeptide repeats (1-YSPTSPS-7) undergo dynamic phosphorylation and dephosphorylation during the transcription cycle to recruit factors that regulate transcription, RNA processing and chromatin modification. We show here that RPRD1A and RPRD1B form homodimers a...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2853
更新日期：2014-08-01 00:00:00
abstract：:Spliceosomes catalyze the maturation of precursor mRNAs in organisms ranging from yeast to humans. Their catalytic core comprises three small nuclear RNAs (U2, U5 and U6) involved in substrate positioning and catalysis. It has been postulated, but never shown experimentally, that the U2-U6 complex adopts at least two ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1672
更新日期：2009-11-01 00:00:00
abstract：:Although t-loops protect telomeres, they are at risk of cleavage by Holliday junction (HJ) resolvases if branch migration converts the three-way t-loop junction into four-way HJs. T-loop cleavage is repressed by the TRF2 basic domain, which binds three- and four-way junctions and protects HJs in vitro. By replacing th...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3451
更新日期：2017-09-01 00:00:00
abstract：:The asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a) acts as a repressive mark that antagonizes trimethylation of H3 lysine 4. Here we report that H3R2 is also symmetrically dimethylated (H3R2me2s) by PRMT5 and PRMT7 and present in euchromatic regions. Profiling of H3-tail interactors by SILAC MS revealed ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2209
更新日期：2012-01-08 00:00:00
abstract：:To locate key RNA features in the structure of the spliceosome by EM, we fused a sequence-specific RNA binding protein to a protein with a distinct donut-shaped structure. We used this fusion to label spliceosomes assembled on a pre-mRNA that contained the target sequence in the exons. The label is clearly visible in ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1378
更新日期：2008-02-01 00:00:00
abstract：:Ubiquitination is a post-translational modification (PTM) that is essential for balancing numerous physiological processes. To enable delineation of protein ubiquitination at a site-specific level, we generated an antibody, denoted UbiSite, recognizing the C-terminal 13 amino acids of ubiquitin, which remain attached ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-018-0084-y
更新日期：2018-07-01 00:00:00
abstract：:Phosphorylation of the spliceosome is essential for RNA splicing, yet how and to what extent kinase signaling affects splicing have not been defined on a genome-wide basis. Using a chemical genetic approach, we show in Schizosaccharomyces pombe that the SR protein kinase Dsk1 is required for efficient splicing of intr...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3057
更新日期：2015-08-01 00:00:00
abstract：:The endosomal sorting complex required for transport (ESCRT) machinery, including ESCRT-III, localizes to the midbody and participates in the membrane-abscission step of cytokinesis. The ESCRT-III protein charged multivesicular body protein 1B (CHMP1B) is required for recruitment of the MIT domain-containing protein s...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1512
更新日期：2008-12-01 00:00:00
abstract：:Celiac disease is a T cell-mediated disease induced by dietary gluten, a component of which is gliadin. 95% of individuals with celiac disease carry the HLA (human leukocyte antigen)-DQ2 locus. Here we determined the T-cell receptor (TCR) usage and fine specificity of patient-derived T-cell clones specific for two epi...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2817
更新日期：2014-05-01 00:00:00
abstract：:Trimethylation of Lys36 in histone H3 (H3K36me3) coordinates events associated with the elongation phase of transcription and is also emerging as an important epigenetic regulator of cell growth and differentiation. We have identified the PWWP domain of bromo and plant homeodomain (PHD) finger-containing protein 1 (BR...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1797
更新日期：2010-05-01 00:00:00
abstract：:The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs undergoing premature termination of translation. It has been argued that in human cells, NMD is restricted to a pioneer round of translation initiated on mRNAs associated with the cap-binding complex (CBC) and that the exchange of the CBC for the eIF4F tran...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2575
更新日期：2013-06-01 00:00:00
abstract：:Although R loops can occur at different genomic locations, the factors that determine their formation and frequency remain unclear. Emerging evidence indicates that DNA breaks stimulate DNA-RNA hybrid formation. Here, we discuss the possibility that formation of hybrids may be an inevitable risk of DNA breaks that occ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3395
更新日期：2017-05-04 00:00:00
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 ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章,评审
doi：10.1038/nsmb.3092
更新日期：2015-11-01 00:00:00
abstract：:During protein synthesis, mRNA and tRNAs are iteratively translocated by the ribosome. Precisely what molecular event is rate limiting for translocation is not known. Here we show that disruption of the interactions between the A-site codon and the ribosome accelerates translocation, suggesting that the release of the...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2140
更新日期：2011-10-23 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：:The interaction of autotaxin with its substrates leads to the production of lysophosphatidic acids (LPA), bioactive lipids with an emerging prominent role in inflammation and cancer. Two papers in this issue tell the previously unknown story of autotaxin, from substrate discrimination to highly efficient local deliver...
journal_title：Nature structural & molecular biology
pub_type： 评论,杂志文章
doi：10.1038/nsmb0211-117
更新日期：2011-02-01 00:00:00
abstract：:In response to stress, cells attenuate global protein synthesis but permit efficient translation of mRNAs encoding heat-shock proteins (HSPs). Although decades have passed since the first description of the heat-shock response, how cells achieve translational control of HSP synthesis remains enigmatic. Here we report ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3010
更新日期：2015-05-01 00:00:00
abstract：:Catalysis by members of the RNase H superfamily of enzymes is generally believed to require only two Mg2+ ions that are coordinated by active-site carboxylates. By examining the catalytic process of Bacillus halodurans RNase H1 in crystallo, however, we found that the two canonical Mg2+ ions and an additional K+ faile...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/s41594-018-0099-4
更新日期：2018-08-01 00:00:00
abstract：:Bacteriophages express proteins that inactivate the CRISPR-Cas bacterial immune system. Here we report the crystal structure of the anti-CRISPR protein AcrF3 in complex with Pseudomonas aeruginosa Cas3 (PaCas3). AcrF3 forms a homodimer that locks PaCas3 in an ADP-bound form, blocks the entrance of the DNA-binding tunn...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.3269
更新日期：2016-09-01 00:00:00
abstract：:Changing environmental conditions and lessening fresh water supplies have sparked intense interest in understanding and manipulating abscisic acid (ABA) signaling, which controls adaptive responses to drought and other abiotic stressors. We recently discovered a selective ABA agonist, pyrabactin, and used it to discov...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1898
更新日期：2010-09-01 00:00:00
abstract：:Inconsistent with prevailing models for nonsense-mediated mRNA decay (NMD) in mammals, the mRNA levels of immunoglobulin-mu (Ig-mu) genes with premature termination codons (PTCs) in the penultimate exon are still reduced by NMD when the intron furthest downstream is deleted. As in yeast, this exon junction complex-ind...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1081
更新日期：2006-05-01 00:00:00
abstract：:STING functions as both an adaptor protein signaling cytoplasmic double-stranded DNA and a direct immunosensor of cyclic diguanylate monophosphate (c-di-GMP). The crystal structures of the C-terminal domain of human STING (STING(CTD)) and its complex with c-di-GMP reveal how STING recognizes c-di-GMP. In response to c...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2332
更新日期：2012-06-24 00:00:00
abstract：:Messenger RNAs produced by splicing are translated more efficiently than those produced from similar intronless precursor mRNAs (pre-mRNAs). The exon-junction complex (EJC) probably mediates this enhancement; however, the specific link between the EJC and the translation machinery has not been identified. The EJC prot...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1321
更新日期：2007-12-01 00:00:00
abstract：:The proteasome is the main ATP-dependent protease in eukaryotic cells and controls the concentration of many regulatory proteins in the cytosol and nucleus. Proteins are targeted to the proteasome by the covalent attachment of polyubiquitin chains. The ubiquitin modification serves as the proteasome recognition elemen...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb814
更新日期：2004-09-01 00:00:00
abstract：:The histone variant macroH2A1 regulates gene expression important for differentiation, stem-cell reprogramming and tumor suppression. Here, we demonstrate that in primary human cells, macroH2A1 participates in two physically and functionally distinct types of chromatin marked by either H3K27me3 or nine histone acetyla...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2903
更新日期：2014-11-01 00:00:00
abstract：:The type III secretion system (T3SS) is a macromolecular 'injectisome' that allows bacterial pathogens to transport virulence proteins into the eukaryotic host cell. This macromolecular complex is composed of connected ring-like structures that span both bacterial membranes. The crystal structures of the periplasmic d...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.1603
更新日期：2009-05-01 00:00:00
abstract：:SUMO processing and deconjugation are essential proteolytic activities for nuclear metabolism and cell-cycle progression in yeast and higher eukaryotes. To elucidate the mechanisms used during substrate lysine deconjugation, SUMO isoform processing and SUMO isoform interactions, X-ray structures were determined for a ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb1168
更新日期：2006-12-01 00:00:00
abstract：:Processing of transcribed precursor ribosomal RNA (pre-rRNA) to a mature state is a conserved aspect of ribosome biogenesis in vivo. We developed an affinity-purification system to isolate and analyze in vivo-formed pre-rRNA-containing ribonucleoprotein (RNP) particles (rRNPs) from wild-type E. coli. We observed that ...
journal_title：Nature structural & molecular biology
pub_type： 杂志文章
doi：10.1038/nsmb.2887
更新日期：2014-10-01 00:00:00
