Abstract:
:Antisense oligodeoxynucleotides (ODNs) have biological activity in treating various forms of cancer. The antisense effects of two types of 20mer ODNs, phosphorothioate-modified ODNs (S-ODNs) and S-ODNs with 12 2'-O-methyl groups (Me-S-ODNs), targeted to sites 109 and 277 of bcl-2 mRNA, were compared. Both types were at least as effective as G3139 (Genta, Inc.) in reducing the level of Bcl-2 protein in T24 cells following a 4 h transfection at a dose of 0.1 micro M. Circular dichroism spectra showed that both types formed A-form duplexes with the complementary RNA, and the melting temperatures were in the order of Me-S-ODN.RNA > normal DNA.RNA > S-ODN.RNA. In comparison with the S-ODN, the Me-S-ODN had reduced toxic growth inhibitory effects, was less prone to bind the DNA-binding domain A of human replication protein A, and was as resistant to serum nucleases. Neither type of oligomer induced apoptosis, according to a PARP-cleavage assay. Hybrids formed with Me-S-ODN sequences were less sensitive to RNase H degradation than those formed with S-ODN sequences. Despite this latter disadvantage, the addition of 2'-O-methyl groups to a phosphorothioate-modified ODN is advantageous because of increased stability of binding and reduced non-specific effects.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Yoo BH,Bochkareva E,Bochkarev A,Mou TC,Gray DMdoi
10.1093/nar/gkh516keywords:
subject
Has Abstractpub_date
2004-04-02 00:00:00pages
2008-16issue
6eissn
0305-1048issn
1362-4962pii
32/6/2008journal_volume
32pub_type
杂志文章abstract::Chromatin modulation at various cis-acting elements is critical for V(D)J recombination during T and B cell development. MARbeta, a matrix-associated region (MAR) located upstream of the T cell receptor beta (TCRbeta) enhancer (Ebeta), serves a crucial role in silencing Ebeta-mediated TCR activation. By DNaseI hyperse...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh807
更新日期:2004-09-15 00:00:00
abstract::The Escherichia coli AlkB protein (EcAlkB) is a DNA repair enzyme which reverses methylation damage such as 1-methyladenine (1-meA) and 3-methylcytosine (3-meC). The mammalian AlkB homologues ALKBH2 and ALKBH3 display EcAlkB-like repair activity in vitro, but their substrate specificities are different, and ALKBH2 is ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks327
更新日期:2012-08-01 00:00:00
abstract::The 338.5 kb of the Escherichia coli genome described here together with previously described segments bring the total of contiguous finished sequence of this genome to > 1 Mb. Of 319 open reading frames (ORFs) found in this 338.5 kb segment, 147 (46%) are potential new genes. The positions of several genes which had ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.12.2105
更新日期:1995-06-25 00:00:00
abstract::The solubility of adult beta-globin chromatin (beta A chromatin) from immature chicken red blood cells can be controlled by the presence or absence of n-butyrate in a cell incubation medium. In the absence of n-butyrate, only a small percentage (approximately 4%) of the total beta A chromatin is in a soluble chromatin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.6.1977
更新日期:1985-03-25 00:00:00
abstract::A number of cysteine-rich proteins have recently been isolated by homology screening, differential library screens, and association with other proteins. In this report, we describe the isolation of the rat cysteine-rich protein from a rat brain library during a search for clones with homology to the delta-opioid recep...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.24.5477
更新日期:1994-12-11 00:00:00
abstract::We have isolated the poly(A) polymerase (PAP) encoding gene pla1 [for poly(A) polymerase] from the fission yeast Schizosaccharomyces pombe. Protein sequence alignments with other poly(A) polymerases reveal that pla1 is more closely related to Saccharomyces cerevisiae PAP than to bovine PAP. The two yeast poly(A) polym...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.13.2585
更新日期:1996-07-01 00:00:00
abstract::The detailed principles of the hierarchical folding of eukaryotic chromosomes have been revealed during the last two decades. Along with structures composing three-dimensional (3D) genome organization (chromatin compartments, topologically associating domains, chromatin loops, etc.), the molecular mechanisms that are ...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkaa261
更新日期:2020-05-21 00:00:00
abstract::Transcription start and termination sites were mapped in the E. coli replication origin, oriC. Outward transcription from within oriC (promoters Pori-r and Pori-l) was found to start in vivo at position 178 for Pori-l and at positions 294 and 304 for Pori-r, respectively. These transcripts were terminated after 100-15...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.6.2479
更新日期:1987-03-25 00:00:00
abstract::The thermal stabilities of the duplexes formed between 4'-thio-modified oligodeoxynucleotides and their DNA and RNA complementary strands were determined and compared with those of the corresponding unmodified oligodeoxynucleotides. A 16mer oligodeoxynucleotide containing 10 contiguous 4'-thiothymidylate modifications...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.21.4117
更新日期:1996-11-01 00:00:00
abstract::We have adapted a method for making libraries of mutations in any specific gene for use in the fission yeast Schizosaccharomyces pombe . This elegant and simple method consists of PCR amplification of the gene of interest, followed by co-transformation of fission yeast with the PCR fragment and a linearized plasmid ve...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.20.4783
更新日期:1998-10-15 00:00:00
abstract::Ribosomal RNA (rRNA) in intact ribosomes is cleaved into discrete products on incubation of reticulocyte lysates or L-cell extracts with ppp(A2'p)3A. Cleavage of rRNA may, therefore, provide a useful assay for 2-5A (ppp)A2'p)nA; n = 2 to 4) or for the presence of a 2-5A-dependent nuclease. The results with reticulocyt...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/9.7.1571
更新日期:1981-04-10 00:00:00
abstract::Genomic DNA methylation profiles exhibit substantial variation within the human population, with important functional implications for gene regulation. So far little is known about the characteristics and determinants of DNA methylation variation among healthy individuals. We performed bioinformatic analysis of high-r...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn122
更新日期:2008-06-01 00:00:00
abstract::Chromosomes in vertebrates are protected at both ends by telomere DNA composed of tandem (TTAGGG)n repeats. DNA replication produces a blunt-ended leading strand telomere and a lagging strand telomere carrying a single-stranded G-rich overhang at its end. The G-rich strand can form G-quadruplex structure in the presen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm203
更新日期:2007-01-01 00:00:00
abstract::Non-coding RNA regulatory elements are important for viral replication, making them promising targets for therapeutic intervention. However, regulatory RNA is challenging to detect and characterise using classical structure-function assays. Here, we present in cell Mutational Interference Mapping Experiment (in cell M...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky152
更新日期:2018-05-18 00:00:00
abstract::Endonucleases that generate double-strand breaks in DNA often possess two identical subunits related by rotational symmetry, arranged so that the active sites from each subunit act on opposite DNA strands. In contrast to many endonucleases, Type IIP restriction enzyme BcnI, which recognizes the pseudopalindromic seque...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr588
更新日期:2011-11-01 00:00:00
abstract::Genomic DNA of calf thymus contains 1.5 times as much 5-methylcytosine as similar sperm DNA, but the major EcoRI repeat fragment from satellite I of thymus contains ten times as much 5-methylcytosine as the corresponding fragment from sperm DNA. Restriction enzyme analyses of the total DNA and the satellite I fragment...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/9.18.4537
更新日期:1981-09-25 00:00:00
abstract::The regions of the polypeptide chain immediately preceding or following an α-helix are known as Nt- and Ct cappings, respectively. Cappings play a central role stabilizing α-helices due to lack of intrahelical hydrogen bonds in the first and last turn. Sequence patterns of amino acid type preferences have been derived...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr879
更新日期:2012-01-01 00:00:00
abstract::The major mRNA degradation pathway involves deadenylation of the target molecule followed by decapping and, finally, 5'-->3' exonuclease digestion of the mRNA body. While yeast factors involved in the decapping and exonuclease degradation steps have been identified, the nature of the factor(s) involved in the deadenyl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.12.2448
更新日期:2001-06-15 00:00:00
abstract::KRAS is one of the most mutated genes in human cancer. It is controlled by a G4 motif located upstream of the transcription start site. In this paper, we demonstrate that 8-oxoguanine (8-oxoG), being more abundant in G4 than in non-G4 regions, is a new player in the regulation of this oncogene. We designed oligonucleo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx1142
更新日期:2018-01-25 00:00:00
abstract::Reagents for proteome research must of necessity be generated by high throughput methods. Aptamers are potentially useful as reagents to identify and quantitate individual proteins, yet are currently produced for the most part by manual selection procedures. We have developed automated selection methods, but must stil...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gnf107
更新日期:2002-10-15 00:00:00
abstract::We present a theory of pluralistic and stochastic gene regulation. To bridge the gap between empirical studies and mathematical models, we integrate pre-existing observations with our meta-analyses of the ENCODE ChIP-Seq experiments. Earlier evidence includes fluctuations in levels, location, activity, and binding of ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw042
更新日期:2016-06-02 00:00:00
abstract::Upstream open reading frame (uORF)-mediated translational inhibition is important in controlling key regulatory genes expression. However, understanding the underlying molecular mechanism of such uORF-mediated control system in vivo is challenging in the absence of an animal model. Therefore, we generated a zebrafish ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr645
更新日期:2011-11-01 00:00:00
abstract::Proteins interacting with pre-mRNAs during early stages of spliceosome formation in a HeLa nuclear extract were investigated by photochemical RNA-protein crosslinking. The level of protein crosslinking to a beta-globin pre-mRNA was positively correlated with the presence of an intron. Proteins of 110,000, 59,000 and 3...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.11.3307
更新日期:1990-06-11 00:00:00
abstract::Tight cell-cycle regulation of the histone H4-K20 methyltransferase PR-Set7 is essential for the maintenance of genome integrity. In mammals, this mainly involves the interaction of PR-Set7 with the replication factor PCNA, which triggers the degradation of the enzyme by the CRL4CDT2 E3 ubiquitin ligase. PR-Set7 is al...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky034
更新日期:2018-04-06 00:00:00
abstract::Sox proteins belong to the HMG box superfamily of DNA-binding proteins and are found throughout the animal kingdom. They are involved in the regulation of such diverse developmental processes as germ layer formation, organ development and cell type specifi-cation. Hence, deletion or mutation of Sox proteins often resu...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/27.6.1409
更新日期:1999-03-15 00:00:00
abstract::RNase E is a 472-kDa homo-tetrameric essential endoribonuclease involved in RNA processing and turnover in Escherichia coli. In its N-terminal half (NTH) is the catalytic active site, as also a substrate 5'-sensor pocket that renders enzyme activity maximal on 5'-monophosphorylated RNAs. The protein's non-catalytic C-...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1152
更新日期:2020-01-24 00:00:00
abstract::Genome browsers are widely used for individually exploring various types of genomic data. A handful of genome browsers offer limited tools for collaboration among multiple users. Here, we describe PBrowse, an integrated real-time collaborative genome browser that enables multiple users to simultaneously view and acces...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1358
更新日期:2017-05-19 00:00:00
abstract::The solution structure of the complex between 4', 6-diamidino-2-phenylindole (DAPI) and DNA oligomer [d(GCGATTCGC)]2, containing a central T.T mismatch, has been characterized by combined use of proton one- and two-dimensional NMR spectroscopy, molecular mechanics and molecular dynamics computations including relaxati...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.20.4706
更新日期:1998-10-15 00:00:00
abstract::DNA strand exchange, the central step of homologous recombination, is considered to occur approximately independently of DNA sequence content. However, certain prokaryotic and eukaryotic genomic loci display either an enhanced or reduced frequency of genetic exchange. Here we show that the Homo sapiens DNA strand exch...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl355
更新日期:2006-05-24 00:00:00
abstract::The mutation patterns at Cas9 targeted sites contain unique information regarding the nuclease activity and repair mechanisms in mammalian cells. However, analytical framework for extracting such information are lacking. Here, we present a novel computational platform called Rational InDel Meta-Analysis (RIMA) that en...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky653
更新日期:2018-09-19 00:00:00