Abstract:
:Exposure to many endogenous and exogenous agents can give rise to DNA alkylation, which constitutes a major type of DNA damage. Among the DNA alkylation products, alkyl phosphotriesters have relatively high frequencies of occurrence and are resistant to repair in mammalian tissues. However, little is known about how these lesions affect the efficiency and fidelity of DNA replication in cells or how the replicative bypass of these lesions is modulated by translesion synthesis DNA polymerases. In this study, we synthesized oligodeoxyribonucleotides containing four pairs (Sp and Rp) of alkyl phosphotriester lesions at a defined site, and examined how these lesions are recognized by DNA replication machinery in Escherichia coli cells. We found that the Sp diastereomer of the alkyl phosphotriester lesions could be efficiently bypassed, whereas the Rp counterparts moderately blocked DNA replication. Moreover, the Sp-methyl phosphotriester induced TT→GT and TT→GC mutations at the flanking TT dinucleotide site, and the induction of these mutations required Ada protein, which is known to remove efficiently the methyl group from the Sp-methyl phosphotriester. Together, our study provided a comprehensive understanding about the recognition of alkyl phosphotriester lesions by DNA replication machinery in cells, and revealed for the first time the Ada-dependent induction of mutations at the Sp-methyl phosphotriester site.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Wu J,Wang P,Wang Ydoi
10.1093/nar/gky140subject
Has Abstractpub_date
2018-05-04 00:00:00pages
4013-4021issue
8eissn
0305-1048issn
1362-4962pii
4920851journal_volume
46pub_type
杂志文章abstract::Allostery is the most direct, rapid and efficient way of regulating protein function, ranging from the control of metabolic mechanisms to signal-transduction pathways. However, an enormous amount of unsystematic allostery information has deterred scientists who could benefit from this field. Here, we present the AlloS...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq1022
更新日期:2011-01-01 00:00:00
abstract::GeneAlign is a coding exon prediction tool for predicting protein coding genes by measuring the homologies between a sequence of a genome and related sequences, which have been annotated, of other genomes. Identifying protein coding genes is one of most important tasks in newly sequenced genomes. With increasing numbe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl307
更新日期:2006-07-01 00:00:00
abstract::Equilibrium and kinetics of thermal melting of yeast 5S ribosomal RNA in aqueous NaCl with or without Mg2+ were investigated by differential thermal melting and temperature jump methods. Two peaks (1 and 2) and a shoulder were observed in each of melting curves at ionic strength I=0.002-0.5 and linearity between each ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.10.3363
更新日期:1983-05-25 00:00:00
abstract::Alternative splicing and polyadenylation were observed pervasively in eukaryotic messenger RNAs. These alternative isoforms could either be consequences of physiological regulation or stochastic noise of RNA processing. To quantify the extent of stochastic noise in splicing and polyadenylation, we analyzed the alterna...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1271
更新日期:2013-02-01 00:00:00
abstract::The multiprotein complexes involved in active dis-ruption of chromatin structure, homologous to yeast SWI/SNF complex, have been described for human and Drosophila cells. In all SWI/SNF-class complexes characterised so far, one of the key components is the SNF5-type protein. Here we describe the isolation of a plant (...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.11.2393
更新日期:1999-06-01 00:00:00
abstract::We have used computer assisted dot matrix and oligonucleotide frequency analyses to identify highly recurring sequence elements of 7-11 base pairs in eukaryotic genes and viral DNAs. Such elements are found much more frequently than expected, often with an average spacing of a few hundred base pairs. Furthermore, the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.4.1835
更新日期:1987-02-25 00:00:00
abstract::A computer program, BRUCE, was developed for the identification of transfer-messenger RNA (tmRNA) genes. The program employs heuristic algorithms to search for a tRNA(Ala)-like secondary structure surrounding a short sequence encoding the tag peptide. In the 57 completely sequenced bacterial genomes where tmRNA genes ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkf459
更新日期:2002-08-01 00:00:00
abstract::Synchronous plasmodia of Physarum polycephalum in DNA synthesis were pulse-labelled with [oH]- thymidine for time periods of 15 seconds up to 9 minutes, or given a 30 seconds pulse followed by chase periods of 9 minutes up to 6 hours. Sedimentation analysis in alkaline sucrose gradients revealed at least five species ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/2.8.1381
更新日期:1975-08-01 00:00:00
abstract::Much effort has long been devoted to unraveling the coordinated cellular response to genotoxic insults. In view of the difficulty of obtaining human biological samples of homogeneous origin, I have established a set of stable human clones where one DNA repair gene has been stably silenced by means of RNA interference....
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm195
更新日期:2007-01-01 00:00:00
abstract::Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic proce...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa088
更新日期:2020-04-17 00:00:00
abstract::In this study, we present the DNA-Binding Site Identifier (DBSI), a new structure-based method for predicting protein interaction sites for DNA binding. DBSI was trained and validated on a data set of 263 proteins (TRAIN-263), tested on an independent set of protein-DNA complexes (TEST-206) and data sets of 29 unbound...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt617
更新日期:2013-09-01 00:00:00
abstract::A 12 bp long GCN4-binding, self-complementary duplex DNA d(CATGACGTCATG)(2) has been investigated by NMR spectroscopy to study the structure and dynamics of the molecule in aqueous solution. The NMR structure of the DNA obtained using simulated annealing and iterative relaxation matrix calculations compares quite clos...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.2.499
更新日期:2001-01-15 00:00:00
abstract::The circadian clock comprises transcriptional feedback loops of clock genes. Cryptochromes are essential components of the negative feedback loop in mammals as they inhibit CLOCK-BMAL1-mediated transcription. We purified mouse CRY1 (mCRY1) protein complexes from Sarcoma 180 cells to determine their roles in circadian ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn1013
更新日期:2009-03-01 00:00:00
abstract::Loading of the replicative ring helicase onto the origin of replication (oriC) is the final outcome of a well coordinated series of events that collectively constitute a primosomal cascade. Once the ring helicase is loaded, it recruits the primase and signals the switch to the polymerization mode. The transient nature...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh628
更新日期:2004-06-01 00:00:00
abstract::A growing body of evidence suggests that siRNA could generate off-target effects through different mechanisms. However, the full impact of off-target gene regulation on phenotypic induction and accordingly on data interpretation in the context of large-scale siRNA library screen has not been reported. Here we report o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki762
更新日期:2005-08-09 00:00:00
abstract::Melanotransferrin (MTf) is a tumor associated antigen found in abundance on the surface of melanoma cells. It is a transferrin-like protein found in low amount in most adult tissues and whose gene is reminiscent of house-keeping genes. With the goal of understanding the regulatory mechanisms which might explain the en...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.11.2853
更新日期:1992-06-11 00:00:00
abstract::Alternative splicing (AS) of pre-mRNAs is an important regulatory mechanism shaping the transcriptome. In plants, only few RNA-binding proteins are known to affect AS. Here, we show that the glycine-rich RNA-binding protein AtGRP7 influences AS in Arabidopsis thaliana. Using a high-resolution RT-PCR-based AS panel, we...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks873
更新日期:2012-12-01 00:00:00
abstract::During the formation of a transcriptionally active macronucleus, ciliated protozoa excise large numbers of interstitial segments of DNA (internal eliminated sequences; IESs) from their chromosomes. In this study we analyze the published sequences of 20 IESs that interrupt surface protein genes of Paramecium and identi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.11.2006
更新日期:1995-06-11 00:00:00
abstract::An improved and simplified protocol for DNA immobilization was developed to enhance DNA-DNA hybridization on microwell plates. Target DNA was immobilized by simple dry-adsorption. Efficiencies of DNA immobilization and retention were enhanced 1.4-6.5 times and 4.2-19.6 times, respectively, compared with a conventional...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.20.4098
更新日期:1996-10-15 00:00:00
abstract::A sequence of 89 nucleotides from rabbit beta-globin mRNA has been determined and is shown to code for residues 107 to 137 of the beta-globin protein. In addition, a sequence heterogeneity has been identified within this 89 nucleotide long sequence which corresponds to a known polymorphic variant of rabbit beta-globin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/3.7.1811
更新日期:1976-07-01 00:00:00
abstract::Post-transcriptional modifications are characteristic features of tRNAs and have been shown in a number of cases to influence both their structural and functional properties, including structure stabilization, amino-acylation and codon recognition. We have developed an approach which allows the investigation of the po...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.3.756
更新日期:1999-02-01 00:00:00
abstract::In a bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP)/transcription factor binding screen, we identified Mycobacterium smegmatis Ms6479 as the first c-di-GMP-responsive transcriptional factor in mycobacteria. Ms6479 could specifically bind with c-di-GMP and recognize the promoters of 37 lipid transport an...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks923
更新日期:2012-12-01 00:00:00
abstract::The budding yeast Saccharomyces cerevisiae is proving to be an useful and accurate model for eukaryotic DNA replication. It contains both DNA polymerase alpha (I) and delta (III). Recently, proliferating cell nuclear antigen (PCNA), which in mammalian cells is an auxiliary subunit of DNA polymerase delta and is essent...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.2.261
更新日期:1990-01-25 00:00:00
abstract::The results of differential expression analyses provide scientists with hundreds to thousands of differentially expressed genes that need to be interpreted in light of the biology of the specific system under study. This requires mapping the genes to functional classifications that can be, for example, the KEGG pathwa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt516
更新日期:2013-07-01 00:00:00
abstract::Nuclear factors NF90 and NF45 form a complex involved in a variety of cellular processes and are thought to affect gene expression both at the transcriptional and translational level. In addition, this complex affects the replication of several viruses through direct interactions with viral RNA. NF90 and NF45 dimerize...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks696
更新日期:2012-10-01 00:00:00
abstract::RNA:5-methylcytosine (m5C) methyltransferases are currently the focus of intense research following a series of high-profile reports documenting their physiological links to several diseases. However, no methods exist which permit the specific analysis of RNA:m5C methyltransferases in cells. Herein, we described how a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1047
更新日期:2020-01-10 00:00:00
abstract::Dictyostelium discoideum is of increasing interest as a model eukaryotic cell because its many attributes have recently been expanded to include improved genetic and biochemical manipulability. The ability to transform Dictyostelium using drug resistance as a selectable marker (1) and to gene target by high frequency ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.14.6617
更新日期:1988-07-25 00:00:00
abstract::The ARF tumour suppressor stabilizes p53 by negatively regulating the E3 ubiquitin ligase MDM2 to promote cell cycle arrest and cell death. However, ARF is also able to arrest cell proliferation by inhibiting ribosome biogenesis. In greater part this is achieved by targeting the transcription termination factor I (TTF...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks198
更新日期:2012-07-01 00:00:00
abstract::We have developed an information repository named SpliceInfo to collect the occurrences of the four major alternative-splicing (AS) modes in human genome; these include exon skipping, 5'-alternative splicing, 3'-alternative splicing and intron retention. The dataset is derived by comparing the nucleotide and protein s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki129
更新日期:2005-01-01 00:00:00
abstract::To efficiently utilize the growing body of available protein localization data, we have developed Organelle DB, a web-accessible database cataloging more than 25,000 proteins from nearly 60 organelles, subcellular structures and protein complexes in 154 organisms spanning the eukaryotic kingdom. Organelle DB is the fi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki071
更新日期:2005-01-01 00:00:00