Abstract:
:DNA mismatches that occur between vector homology arms and chromosomal target sequences reduce gene targeting frequencies in several species; however, this has not been reported in human cells. Here we demonstrate that even a single mismatched base pair can significantly decrease human gene targeting frequencies. In addition, we show that homology arm polymorphisms can be used to direct allele-specific targeting or to improve unfavorable vector designs that introduce deletions.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Deyle DR,Li LB,Ren G,Russell DWdoi
10.1093/nar/gkt1303subject
Has Abstractpub_date
2014-03-01 00:00:00pages
3119-24issue
5eissn
0305-1048issn
1362-4962pii
gkt1303journal_volume
42pub_type
杂志文章abstract::Many bacterial plasmids replicate by an asymmetric rolling-circle mechanism that requires sequence-specific recognition for initiation, nicking of one of the template DNA strands and unwinding of the duplex prior to subsequent leading strand DNA synthesis. Nicking is performed by a replication-initiation protein (Rep)...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw689
更新日期:2016-10-14 00:00:00
abstract::We have determined the complete nucleotide sequence of the hormonally regulated yolk protein 1 (YP1) gene of Drosophila melanogaster. We have also determined the sequence location of the 5' and 3' ends of both the mature mRNA and the gene's only intron. The YP1 gene contains sequences similar to those found in many ot...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/9.23.6407
更新日期:1981-12-11 00:00:00
abstract::Despite the large number of noncoding RNAs in human genome and their roles in many diseases include cancer, we know very little about them due to lack of structural clues. The centerpiece of the structural clues is the full RNA base-pairing structure of secondary and tertiary contacts that can be precisely obtained on...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1192
更新日期:2020-02-20 00:00:00
abstract::Enzymes that form transient DNA-protein covalent complexes are targets for several potent classes of drugs used to treat infectious disease and cancer, making it important to establish robust and rapid procedures for analysis of these complexes. We report a method for isolation of DNA-protein adducts and their identif...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku490
更新日期:2014-07-01 00:00:00
abstract::The environmental carcinogen benzo[a]pyrene (BP) is metabolized to reactive diol epoxides that bind to cellular DNA by predominantly forming N2-guanine adducts (G*). Mutation hotspots for these adducts are frequently found in 5'- ... GG ... dinucleotide sequences, but their origins are poorly understood. Here we used ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm022
更新日期:2007-01-01 00:00:00
abstract::The modified nucleoside, 7-(4,5-cis-dihydroxy-1-cyclopenten-3-yl-aminomethyl)-7-deazaguanosine, designated as Q, and its derivative, Q*, were found in tRNA's from various organisms, including several mammalian tissues, other animals such as starfish, lingula and hagfish, and wheat germ. Q isolated from rat liver tRNA ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/2.10.1931
更新日期:1975-10-01 00:00:00
abstract::Nucleosomes are the most abundant protein-DNA complexes in eukaryotes that provide compaction of genomic DNA and are implicated in regulation of transcription, DNA replication and repair. The details of DNA positioning on the nucleosome and the DNA conformation can provide key regulatory signals. Hydroxyl-radical foot...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx616
更新日期:2017-09-19 00:00:00
abstract::In a gene targeting experiment, the generation of a targeting construct often requires complex DNA manipulations. We developed a set of cassettes and plasmids useful for creating targeting vectors to modify the mammalian genome. A positive selection marker cassette (PGK/EM7p-npt), which included dual prokaryotic and e...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gni055
更新日期:2005-03-22 00:00:00
abstract::The frequencies of occurrence of four bases in the first, second and third codon positions and in the total coding sequences have been calculated by the codon usage table published in 1990 by Ikemura et al. The distribution of frequencies are further analysed in detail by a graphic technique presented recently by us. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.22.6313
更新日期:1991-11-25 00:00:00
abstract::The database of 3D interacting domains (3did) is a collection of protein interactions for which high-resolution 3D structures are known. 3did exploits structural information to provide the crucial molecular details necessary for understanding how protein interactions occur. Besides interactions between globular domain...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn690
更新日期:2009-01-01 00:00:00
abstract::Single-molecule force spectroscopy provides insight into how proteins bind to and move along DNA. Such studies often embed a single-stranded (ss) DNA region within a longer double-stranded (ds) DNA molecule. Yet, producing these substrates remains laborious and inefficient, particularly when using the traditional thre...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx761
更新日期:2017-10-13 00:00:00
abstract::Many RNP proteins contain one or more copies of the RNA recognition motif (RRM) and are thought to be involved in cellular RNA metabolism. We have previously characterized in Xenopus a nervous system specific gene, nrp1, that is more similar to the hnRNP A/B proteins than to other known proteins (K. Richter, P. J. Goo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.4.999
更新日期:1993-02-25 00:00:00
abstract::Chemically modified antisense oligonucleotides (ASOs) with phosphorothioate (PS) linkages have been extensively studied as research and therapeutic agents. PS-ASOs can enter the cell and trigger cleavage of complementary RNA by RNase H1 even in the absence of transfection reagent. A number of cell surface proteins hav...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky145
更新日期:2018-04-20 00:00:00
abstract::DNA transposon-based vectors have emerged as gene vehicles with a wide biomedical and therapeutic potential. So far, genomic insertion of such vectors has relied on the co-delivery of genetic material encoding the gene-inserting transposase protein, raising concerns related to persistent expression, insertional mutage...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1163
更新日期:2014-02-01 00:00:00
abstract::A new method is reported for the synthesis of oligodeoxyribonucleotides containing 2-aminopurine residues at selected sites. This method involves protection of the 2-aminopurine ribonucleoside, reduction to the deoxyribonucleoside and standard preparation of the 5'-0- (4,4'-dimethoxytrityl)-3'-O-(2-cyanoethyl)-N,N- di...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.4.754
更新日期:1996-02-15 00:00:00
abstract::Recently, a family of transcription factors structurally related to Sp1 has been described; thus, more than one activator may bind to the GC boxes present in a number of viral and cellular promoters. We have compared the transactivation potentials of Sp1, Sp3 and Sp4 proteins on the human immunodeficiency virus type 1...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.23.4914
更新日期:1994-11-25 00:00:00
abstract::Phenotype analysis is commonly recognized to be of great importance for gaining insight into genetic interaction underlying inherited diseases. However, few computational contributions have been proposed for this purpose, mainly owing to lack of controlled clinical information easily accessible and structured for comp...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki454
更新日期:2005-07-01 00:00:00
abstract::Activation of the transcription factor NF-kappaB is critical for the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory response. Here we report the complete gene expression profile from activated microvascular endothelial cells emphasizing the direct contribution of the NF-kappaB pathway. Human microvascula...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki836
更新日期:2005-09-21 00:00:00
abstract::Alterations in cancer genomes strongly influence clinical responses to treatment and in many instances are potent biomarkers for response to drugs. The Genomics of Drug Sensitivity in Cancer (GDSC) database (www.cancerRxgene.org) is the largest public resource for information on drug sensitivity in cancer cells and mo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1111
更新日期:2013-01-01 00:00:00
abstract::The molecular mechanisms that underlie the neurological manifestations of patients with inherited diseases of vitamin B12 (cobalamin) metabolism remain to date obscure. We observed transcriptomic changes of genes involved in RNA metabolism and endoplasmic reticulum stress in a neuronal cell model with impaired cobalam...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky634
更新日期:2018-09-06 00:00:00
abstract::We have constructed a stable cell line, human embryonal kidney 293M+, containing a lacZ reporter gene controlled by an in vitro methylated hormone-responsive enhancer. Methylation of the enhancer-promoter abolishes lacZ expression controlled by ponasterone A (an analogue of ecdysone). Ponasterone A-induced expression ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.17.3603
更新日期:2001-09-01 00:00:00
abstract::A multivariate statistical method called correspondence analysis was used to examine the codon usage of one-hundred-and-one nuclear genes of maize (Zea mays L.). Forty percent of the variation in codon usage was due to bias toward G or C-ending versus A or U-ending codons. Differences in levels of G-ending codons show...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.23.5294
更新日期:1993-11-25 00:00:00
abstract::The spatio-temporal organization of chromatin in the eukaryotic cell nucleus is of vital importance for transcription, DNA replication and genome maintenance. Each of these activities is tightly regulated in both time and space. While we have a good understanding of chromatin organization in space, for example in fixe...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkaa135
更新日期:2020-04-17 00:00:00
abstract::The 'druggable genome' encompasses several protein families, but only a subset of targets within them have attracted significant research attention and thus have information about them publicly available. The Illuminating the Druggable Genome (IDG) program was initiated in 2014, has the goal of developing experimental...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1072
更新日期:2017-01-04 00:00:00
abstract::The polyadenylate binding protein 1 (PABPN1) is a ubiquitously expressed RNA binding protein vital for multiple steps in RNA metabolism. Although PABPN1 plays a critical role in the regulation of RNA processing, mutation of the gene encoding this ubiquitously expressed RNA binding protein causes a specific form of mus...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx786
更新日期:2017-10-13 00:00:00
abstract::Transcription of the human adenovirus 5 genome in transformed rat embryo cells (DFK3) was investigated using two different approaches. Preferential digestion of transcribed viral sequences by DNase I was analysed using kinetics of renaturation of 32P-labeled Ad5 HpaI restriction fragments in the presence of material w...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/5.1.1
更新日期:1978-01-01 00:00:00
abstract::In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data available through NCBI's web site. NCBI resources include Entrez, the Entrez Programming Utiliti...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm1000
更新日期:2008-01-01 00:00:00
abstract::We present a multi-laboratory effort to describe the structural and dynamical properties of duplex B-DNA under physiological conditions. By processing a large amount of atomistic molecular dynamics simulations, we determine the sequence-dependent structural properties of DNA as expressed in the equilibrium distributio...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz905
更新日期:2019-12-02 00:00:00
abstract::We have analyzed the molecular mechanism that makes translation of the MS2 replicase cistron dependent on the translation of the upstream coat cistron. Deletion mapping on cloned cDNA of the phage shows that the ribosomal binding site of the replicase cistron is masked by a long distance basepairing to an internal coa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.19.6955
更新日期:1985-10-11 00:00:00
abstract::The integrases are a diverse family of tyrosine recombinases which rearrange DNA duplexes by means of conservative site-specific recombination reactions. Members of this family, of which the well-studied lambda Int protein is the prototype, were previously found to share four strongly conserved residues, including an ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.18.3605
更新日期:1997-09-15 00:00:00