Abstract:
:Chromosome stability is primarily determined by telomere length. TRF1 is the core subunit of shelterin that plays a critical role in telomere organization and replication. However, the dynamics of TRF1 in scenarios of telomere-processing activities remain elusive. Using single-molecule magnetic tweezers, we here investigated the dynamics of TRF1 upon organizing a human telomere and the protein-DNA interactions at a moving telomeric fork. We first developed a method to obtain telomeres from human cells for directly measuring the telomere length by single-molecule force spectroscopy. Next, we examined the compaction and decompaction of a telomere by TRF1 dimers. TRF1 dissociates from a compacted telomere with heterogenous loops in ∼20 s. We also found a negative correlation between the number of telomeric loops and loop sizes. We further characterized the dynamics of TRF1 at a telomeric DNA fork. With binding energies of 11 kBT, TRF1 can modulate the forward and backward steps of DNA fork movements by 2-9 s at a critical force of F1/2, temporarily maintaining the telomeric fork open. Our results shed light on the mechanisms of how TRF1 organizes human telomeres and facilitates the efficient replication of telomeric DNA. Our work will help future research on the chemical biology of telomeres and shelterin-targeted drug discovery.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Li X,Wang M,Zheng W,Huang W,Wang Z,Jin K,Liu L,Yu Zdoi
10.1093/nar/gkaa1222subject
Has Abstractpub_date
2021-01-25 00:00:00pages
760-775issue
2eissn
0305-1048issn
1362-4962pii
6042956journal_volume
49pub_type
杂志文章abstract::The ever growing number of completely sequenced prokaryotic genomes facilitates cross-species comparisons by genomic annotation algorithms. This paper introduces a new probabilistic framework for comparative genomic analysis and demonstrates its utility in the context of improving the accuracy of prokaryotic gene star...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkf423
更新日期:2002-07-15 00:00:00
abstract::The multifunctional HCV core protein consists of a hydrophilic RNA interacting D1 domain and a hydrophobic D2 domain interacting with membranes and lipid droplets. The core D1 domain was found to possess nucleic acid annealing and strand transfer properties. To further understand these chaperone properties, we investi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq094
更新日期:2010-06-01 00:00:00
abstract::We have previously reported the human cDNA encoding MSSP-1, a sequence-specific double- and single-stranded DNA binding protein [Negishi, Nishita, Saëgusa, Kakizaki, Galli, Kihara, Tamai, Miyajima, Iguchi-Ariga and Ariga (1994) Oncogene, 9, 1133-1143]. MSSP-1 binds to a DNA replication origin/transcriptional enhancer ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.25.5576
更新日期:1994-12-25 00:00:00
abstract::A recently reported cDNA clone coding for human promyelocytic L apoferritin, shows some differences with a liver L apoferritin cDNA. We have investigated if these differences are due to the expression of different genes or to an alternative transcription of an unique gene. In this paper we report data suggesting that ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.7.2863
更新日期:1986-04-11 00:00:00
abstract::RNA processing is critical for proper spatial and temporal control of gene expression. The ubiquitous nuclear polyadenosine RNA binding protein, PABPN1, post-transcriptionally regulates multiple steps of gene expression. Mutations in the PABPN1 gene expanding an N-terminal alanine tract in the PABPN1 protein from 10 a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky535
更新日期:2018-09-06 00:00:00
abstract::Since 2010, the Genomicus web server is available online at http://genomicus.biologie.ens.fr/genomicus. This graphical browser provides access to comparative genomic analyses in four different phyla (Vertebrate, Plants, Fungi, and non vertebrate Metazoans). Users can analyse genomic information from extant species, as...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx1003
更新日期:2018-01-04 00:00:00
abstract::Dramatic improvements in ribozyme mimics have been achieved by employing the principles of small molecule catalysis to the design of macromolecular, biomimetic reagents. Ribozyme mimics derived from the ligand 2,9-dimethylphenanthroline (neocuproine) show at least 30-fold improvements in efficiency at sequence-specifi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.10.2199
更新日期:2001-05-15 00:00:00
abstract::Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx693
更新日期:2017-09-19 00:00:00
abstract::The viral RNA (vRNA) genome of influenza viruses is replicated by the RNA-dependent RNA polymerase (RNAP) via a complementary RNA (cRNA) intermediate. The vRNA promoter can adopt multiple conformations when bound by the RNAP. However, the dynamics, determinants, and biological role of these conformations are unknown; ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz313
更新日期:2019-07-09 00:00:00
abstract::A fundamental problem with applying Consensus, Weight-Matrix or hidden Markov models as search tools for biosequences is that there is no way to know, from the model, if the modeled sequences display any dependencies between positional identities. In some instances, these dependencies are crucial in correctly acceptin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki374
更新日期:2005-07-01 00:00:00
abstract::A novel method for sequence specific double strand DNA cleavage using PNA (peptide nucleic acid) targeting is described. Nuclease S1 digestion of double stranded DNA gives rise to double strand cleavage at an occupied PNA strand displacement binding site, and under optimized conditions complete cleavage can be obtaine...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.9.2103
更新日期:1993-05-11 00:00:00
abstract::The European Nucleotide Archive (ENA; https://www.ebi.ac.uk/ena), provided from EMBL-EBI, has for more than three decades been responsible for archiving the world's public sequencing data and presenting this important resource to the scientific community to support and accelerate the global research effort. Here, we o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky1078
更新日期:2019-01-08 00:00:00
abstract::The development of genetic switches and their integrated forms (genetic circuits) with desired specifications/functions is key for success in synthetic biology. Due to the difficulty in rational design, genetic switches and circuits with desirable specifications are mostly obtained by directed evolution. Based on a vi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq1070
更新日期:2011-02-01 00:00:00
abstract::Two fragments cloned from purified human satellite III DNA do not cross-react with each other. One fragment, for which a partial sequence is reported, hybridises to satellite II as well as III and is shown to originate on chromosome 1. The other cloned fragment originates from the Y chromosome. This fragment has under...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.10.3177
更新日期:1979-07-25 00:00:00
abstract::HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at approximately 2.5-3.0 A resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn464
更新日期:2008-09-01 00:00:00
abstract::The Saccharomyces cerevisiae Sgs1p helicase localizes to the nucleolus and is required to maintain the integrity of the rDNA repeats. Sgs1p is a member of the RecQ DNA helicase family, which also includes Schizo-saccharomyces pombe Rqh1, and the human BLM and WRN genes. These genes encode proteins which are essential ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.9.1978
更新日期:1999-05-01 00:00:00
abstract::The secondary structure of an adenovirus associated low molecular weight RNA (VAI-RNA) has been studied by partial digestion with T1-RNase and S1-endonuclease followed by T1-fingerprint analysis. The empirical secondary structure has been compared with two computer generated models based on minimal free energy of the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/9.17.4239
更新日期:1981-09-11 00:00:00
abstract::Homing endonucleases (HEs) cut long DNA target sites with high specificity to initiate and target the lateral transfer of mobile introns or inteins. This high site specificity of HEs makes them attractive reagents for gene targeting to promote DNA modification or repair. We have generated several hundred catalytically...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp004
更新日期:2009-04-01 00:00:00
abstract::An efficient procedure for the synthesis of unnatural alpha-anomeric oligodeoxyribonucleotides is described. This solid-phase procedure is based on the use of alpha-nucleoside phosphoramidites and alpha-nucleoside derivatized solid supports corresponding to the four natural bases and allow rapid synthesis of oligonucl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.3.833
更新日期:1988-02-11 00:00:00
abstract::DNA adenine methyltransferase (Dam) is widespread and conserved among the γ-proteobacteria. Methylation of the Ade in GATC sequences regulates diverse bacterial cell functions, including gene expression, mismatch repair and chromosome replication. Dam also controls virulence in many pathogenic Gram-negative bacteria. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv251
更新日期:2015-04-30 00:00:00
abstract::Selenocysteine (Sec), the 21(st) amino acid in translation, uses its specific tRNA (tRNA(Sec)) to recognize the UGA codon. The Sec-specific elongation factor SelB brings the selenocysteinyl-tRNA(Sec) (Sec-tRNA(Sec)) to the ribosome, dependent on both an in-frame UGA and a Sec-insertion sequence (SECIS) in the mRNA. Th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv833
更新日期:2015-10-15 00:00:00
abstract::The extent of base pairing in Escherichia coli and Bacillus stearothermophilus 5S RNAs was determined by infrared spectroscopy. From the infrared spectra taken at 20 degrees and 52 degrees C it is concluded that E. coli and B. stearothermophlius 5S RNAs possess a large number of base pairs (Table I). Comparison of our...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/7.4.1043
更新日期:1979-10-25 00:00:00
abstract::We attempted to use the polymerase chain reaction (PCR) to monitor in vitro recombination in a plasmid containing directly repeated sequences. Some of the plasmid preparations which had not been exposed to recombination conditions were however found to behave in the PCR test as if they had undergone homologous recombi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.9.2423
更新日期:1991-05-11 00:00:00
abstract::Many types of DNA structures are generated in response to DNA damage, repair and recombination that require processing via specialized nucleases. DNA hairpins represent one such class of structures formed during V(D)J recombination, palindrome extrusion, DNA transposition and some types of double-strand breaks. Here w...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr1059
更新日期:2012-03-01 00:00:00
abstract::Leishmania species are protozoan parasites whose remarkably plastic genome limits the establishment of effective genetic manipulation and leishmaniasis treatment. The strategies used by Leishmania to maintain its genome while allowing variability are not fully understood. Here, we used DiCre-mediated conditional gene ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky1017
更新日期:2018-12-14 00:00:00
abstract::The interactions between beef tRNATrp with avian myeloblastosis reverse transcriptase have been studied by statistical chemical modifications of phosphate (ethylnitrosourea) and cytidine (dimethyl sulfate) residues, as well as by digestion of complexed tRNA by Cobra venom nuclease and Neurospora crassa endonuclease. R...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.5.2259
更新日期:1984-03-12 00:00:00
abstract::RegulonDB is a DataBase that integrates biological knowledge of the mechanisms that regulate the transcription initiation in Escherichia coli , as well as knowledge on the organization of the genes and regulatory signals into operons in the chromosome. The operon is the basic structure used in RegulonDB to describe th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.1.55
更新日期:1998-01-01 00:00:00
abstract::Expression of a proof-reading deficient form of mitochondrial DNA (mtDNA) polymerase gamma, POLG, causes early death accompanied by features of premature ageing in mouse. However, the mechanism of cellular senescence remains unresolved. In addition to high levels of point mutations of mtDNA, the POLG mutator mouse har...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp091
更新日期:2009-04-01 00:00:00
abstract::Identification of MHC-binding peptides is a prerequisite in rational design of T-cell based peptide vaccines. During the past decade a number of computational approaches have been introduced for the prediction of MHC-binding peptides, efficiently reducing the number of candidate binders that need to be experimentally ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl284
更新日期:2006-07-01 00:00:00
abstract::The transcription regulator, tvMyb1, is the first Myb family protein identified in Trichomonas vaginalis. Using an electrophoretic mobility shift assay, we defined the amino-acid sequence from Lys(35) to Ser(141) (tvMyb1(35-141)) as the minimal DNA-binding domain, encompassing two Myb-like DNA-binding motifs (designat...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp097
更新日期:2009-04-01 00:00:00