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. I used pEBVsiRNA plasmids that greatly enhance long-term gene silencing in human cells. My older clones reached >500 days in culture. Knock-down HeLa clones maintained a gene silencing phenotype for an extended period in culture, demonstrating that I was able to mimic cells from cancer-prone syndromes. I have silenced >20 genes acting as sensors/transducers (ATM, ATR, Rad50, NBS1, MRE11, PARG and KIN17), or of different DNA repair pathways. In HeLa cells, I have switched off the expression of genes involved in nucleotide excision repair (XPA, XPC, hHR23A, hHR23B, CSA and CSB), nonhomologous end-joining (DNA-PKcs, XRCC4 and Ligase IV), homologous recombination repair (Rad51 and Rad54), or base excision repair (Ogg1 and Ligase III). These cells displayed the expected DNA repair phenotype. We could envisage untangling the complex network between the different DNA repair pathways. In this study, no viral vehicles, with their attendant ethical and safety concerns, were used.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Biard DSdoi
10.1093/nar/gkm195subject
Has Abstractpub_date
2007-01-01 00:00:00pages
3535-50issue
11eissn
0305-1048issn
1362-4962pii
gkm195journal_volume
35pub_type
杂志文章abstract::The smallest catalytic RNA identified to date is a manganese-dependent ribozyme that requires only a complex between GAAA and UUU to effect site-specific cleavage. We show here that this ribozyme occurs naturally in the 3'-UTR of Vg1 and beta-actin mRNAs. In accord with earlier studies with model RNAs, cleavage occurs...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn530
更新日期:2008-10-01 00:00:00
abstract::The base excision repair DNA glycosylase MutY homolog (MYH) is responsible for removing adenines misincorporated into DNA opposite guanine or 7,8-dihydro-8-oxo-guanine (8-oxoG), thereby preventing G:C to T:A mutations. Biallelic germline mutations in the human MYH gene predispose individuals to multiple colorectal ade...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki209
更新日期:2005-01-26 00:00:00
abstract::The function of non-coding RNA genes largely depends on their secondary structure and the interaction with other molecules. Thus, an accurate prediction of secondary structure and RNA-RNA interaction is essential for the understanding of biological roles and pathways associated with a specific RNA gene. We present web...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr248
更新日期:2011-07-01 00:00:00
abstract::Human Hepatitis B Virus (HBV) RNAs contain a cis -acting sequence, the post-transcriptional regulatory element (HPRE), which facilitates the cytoplasmic localization of intronless transcripts. Our previous studies have shown that the HPRE is composed of at least two independent sub-elements, HPREalpha and HPREbeta, wh...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.21.4818
更新日期:1998-11-01 00:00:00
abstract::Prokaryotes evolved numerous systems that defend against predation by bacteriophages. In addition to well-known restriction-modification and CRISPR-Cas immunity systems, many poorly characterized systems exist. One class of such systems, named BREX, consists of a putative phosphatase, a methyltransferase and four othe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky1125
更新日期:2019-01-10 00:00:00
abstract::The antitumor antibiotic CC-1065 binds in the minor groove of double-stranded DNA, and the cyclopropapyrroloindole (CPI) subunit of the drug alkylates adjacent adenines at their N-3 position. We have attached racemic CPI to oligodeoxyribonucleotides (ODNs) via a terminal phosphorothioate at either the 3'- or 5'-end of...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.4.683
更新日期:1996-02-15 00:00:00
abstract::Advances in genomic sequencing have enormous potential to revolutionize personalized medicine, however distinguishing disease-causing from benign variants remains a challenge. The increasing number of human genome and exome sequences available has revealed areas where unfavourable variation is removed through purifyin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz457
更新日期:2019-07-02 00:00:00
abstract::The nucleotide sequence of a Pseudomonas trans-zeatin producing gene (ptz) from the pCK1 plasmid of Pseudomonas syringae pv. savastanoi strain 1006 has been determined. This gene confers upon E. coli the ability to synthesize and secrete several cytokinins including trans-zeatin, iso-pentenyladenine and their respecti...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.6.2555
更新日期:1986-03-25 00:00:00
abstract::Hepatitis B viruses, or hepadnaviruses, are small DNA-containing viruses that replicate through reverse transcription. Their prototype, HBV, causes severe liver disease in humans. The hepadnaviral P protein is an unusual reverse transcriptase (RT) that initiates DNA synthesis by host-factor-dependent protein priming o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.7.1679
更新日期:2002-04-01 00:00:00
abstract::We investigate the mechanistic nature of the Snf2 family protein HARP, mutations of which are responsible for Schimke immuno-osseous dysplasia. Using a single-molecule magnetic tweezers assay, we construct RPA-stabilized DNA bubbles within torsionally constrained DNA to investigate the annealing action of HARP on a ph...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx147
更新日期:2017-05-05 00:00:00
abstract::Genetic recombination in meiosis plays an important role in generating diversity of genetic information. In yeast an Escherichia coli RecA-like gene, DMC1, is expressed in meiotic prophase and its product co-localizes with Rad51 protein on zygotene chromosomes. We have cloned the mouse and human homologs of the yeast ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.3.470
更新日期:1996-02-01 00:00:00
abstract::Owing to their great potentials in genetic code extension and the development of nucleic acid-based functional nanodevices, DNA duplexes containing HgII-mediated base pairs have been extensively studied during the past 60 years. However, structural basis underlying these base pairs remains poorly understood. Herein, w...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1296
更新日期:2017-03-17 00:00:00
abstract::TIAR and HuR are mRNA-binding proteins that play important roles in the regulation of translation. They both possess three RNA recognition motifs (RRMs) and bind to AU-rich elements (AREs), with seemingly overlapping specificity. Here we show using SPR that TIAR and HuR bind to both U-rich and AU-rich RNA in the nanom...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq837
更新日期:2011-02-01 00:00:00
abstract::Hg-UMP-containing transcripts made from chick erythroid chromatins with E. coli RNA polymerase hybridize to chick globin cDNA. Contamination with endogenous globin RNA has been largely removed by purification on SH-agarose columns at 55 degrees C. Some endogenous globin mRNA sequences remain, probably as hybrids with ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/5.4.1237
更新日期:1978-04-01 00:00:00
abstract::The database of molecular motions, MolMovDB (http://molmovdb.org), has been in existence for the past decade. It classifies macromolecular motions and provides tools to interpolate between two conformations (the Morph Server) and predict possible motions in a single structure. In 2005, we expanded the services offered...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkj046
更新日期:2006-01-01 00:00:00
abstract::Through a computer search of DNA databases, we have identified the homologs of the mgU6-47 snoRNA gene from the yeast Schizosaccharomyces pombe, the fly Drosophila melanogaster and human. The three box C/D-containing snoRNA genes showed no significant similarity in their sequences except for an 11 nt long complementar...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.4.894
更新日期:2002-02-15 00:00:00
abstract::In plant organelles, RNA editing alters specific cytidine residues to uridine in transcripts. All of the site-specificity factors of RNA editing identified so far are pentatricopeptide repeat (PPR) proteins. A defect in a specific PPR protein often impairs RNA editing at multiple sites, at which the cis-acting element...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks164
更新日期:2012-06-01 00:00:00
abstract::Pre-mRNA transcripts in a variety of organisms, including plants, Drosophila and Caenorhabditis elegans, contain introns which are significantly richer in adenosine and uridine residues than their flanking exons. Previous analyses using exonic and intronic replacements between two nonequivalent 5'splice sites in the 4...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.5.1071
更新日期:1997-03-01 00:00:00
abstract::TOP mRNAs are vertebrate transcripts which contain a 5'terminal oligopyrimidine tract (5'TOP), encode for ribosomal proteins and elongation factors 1alpha and 2, and are candidates for growth-dependent translational control mediated through their 5'TOP. In the present study we show that elongation factor 2 (EF2) mRNA ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.5.995
更新日期:1997-03-01 00:00:00
abstract::We describe an algorithm for gene identification in DNA sequences derived from shotgun sequencing of microbial communities. Accurate ab initio gene prediction in a short nucleotide sequence of anonymous origin is hampered by uncertainty in model parameters. While several machine learning approaches could be proposed t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq275
更新日期:2010-07-01 00:00:00
abstract::Unrepaired DNA damage may arrest ongoing replication forks, potentially resulting in fork collapse, increased mutagenesis and genomic instability. Replication through DNA lesions depends on mono- and polyubiquitylation of proliferating cell nuclear antigen (PCNA), which enable translesion synthesis (TLS) and template ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks850
更新日期:2012-11-01 00:00:00
abstract::Mitochondrial DNA is a sensitive target of chemical carcinogens (Backer and Weinstein (1980) Science 209, 297-299), suggesting that mutations of the mitochondrial genome occur in tumor cells. We examined this point by comparing mitochondrial DNA sequences in four rat tumors with those of normal rat liver. Some novel m...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.6.1635
更新日期:1983-03-25 00:00:00
abstract::Major efforts are underway to elucidate the spatial distribution of ribosomal RNAs (rRNAs) in the ribosome. An especially informative approach is the identification of likely base-base tertiary interactions within the RNA by phylogenetic comparison. Herein evidence is presented for three heretofore unrecognized candid...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.6.2215
更新日期:1989-03-25 00:00:00
abstract::Here we report that the poor binding of methylphosphonate oligodeoxynucleosides (MP-ODNs) to their nucleic acid targets can be improved by additional inversion of the anomeric configuration (from beta to alpha) in the sugar moieties to give a new class of analogs, MP alpha-oligonucleosides. MP alpha-dT12and MP 5' alph...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.20.4551
更新日期:1998-10-15 00:00:00
abstract::The mitochondrial DNA of Neurospora crassa has a heterogeneous intramolecular base distribution. A contiguous piece, representing at least 30% of the total genome, has a G+C content that is 6% lower than the overall G+C content of the DNA. The genes for both ribosomal RNAs are contained in the remaining, relatively G+...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.1.129
更新日期:1977-01-01 00:00:00
abstract::Chicken erythrocyte inner histones (H2A, H2B, H3 and H4) were associated with the two complementary homopolymeric polydeoxyribonucleotides and the two alternating copolymeric polydeoxyribonucleotides. No evidence for formation of chromatin-like structures was obtained for the complexes with poly(dG) . poly(dC) or poly...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.4.1387
更新日期:1979-04-01 00:00:00
abstract::Three Rat1/Xrn2 homologues exist in Arabidopsis thaliana: nuclear AtXRN2 and AtXRN3, and cytoplasmic AtXRN4. The latter has a role in degrading 3' products of miRNA-mediated mRNA cleavage, whereas all three proteins act as endogenous post-transcriptional gene silencing suppressors. Here we show that, similar to yeast ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq172
更新日期:2010-07-01 00:00:00
abstract::The TcSNP database (http://snps.tcruzi.org) integrates information on genetic variation (polymorphisms and mutations) for different stocks, strains and isolates of Trypanosoma cruzi, the causative agent of Chagas disease. The database incorporates sequences (genes from the T. cruzi reference genome, mRNAs, ESTs and ge...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn874
更新日期:2009-01-01 00:00:00
abstract::We cloned and sequenced a portion of chloroplast DNA from the hornwort Anthoceros formosae. A nucleotide sequence of 7556 bp contained structures similar to those of ndhK, ndhC, trnV, trnM, atpE, atpB, rbcL, trnR and accD. The arrangement of these was the same as that of other chloroplast DNA. However, two nonsense co...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.6.1008
更新日期:1996-03-15 00:00:00
abstract::Knowledge of subcellular localizations (SCLs) of plant proteins relates to their functions and aids in understanding the regulation of biological processes at the cellular level. We present PlantLoc, a highly accurate and fast webserver for predicting the multi-label SCLs of plant proteins. The PlantLoc server has two...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt428
更新日期:2013-07-01 00:00:00