Abstract:
:The prime mechanism by which p53 acts as a tumor suppressor is as a transcription factor regulating the expression of diverse downstream genes. The DNA-binding domain of p53 (p53DBD) interacts with defined DNA sites and is the main target for mutations in human primary tumors. Here, we show that the CWWG motif, found in the center of each consensus p53 half-site, is a key player in p53/DNA interactions. Gel-mobility-shift assays provide a unique opportunity to directly observe the various oligomeric complexes formed between p53DBD and its target sites. We demonstrate that p53DBD binds to p53 consensus sites containing CATG with relatively low cooperativity, as both dimers and tetramers, and with even lower cooperativity to such sites containing spacer sequences. p53DBD binds to sites containing CAAG and CTAG with measurable affinity only when imbedded in two contiguous p53 half-sites and only as tetramers (with very high cooperativity). There are three orders-of-magnitude difference in the cooperativity of interaction between sites differing in their non-contacted step, and further two orders-of-magnitude difference as a function of spacer sequences. By experimentally measuring the global structural properties of these sites, by cyclization kinetics of DNA minicircles, we correlate these differences with the torsional flexibility of the binding sites.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Beno I,Rosenthal K,Levitine M,Shaulov L,Haran TEdoi
10.1093/nar/gkq1044subject
Has Abstractpub_date
2011-03-01 00:00:00pages
1919-32issue
5eissn
0305-1048issn
1362-4962pii
gkq1044journal_volume
39pub_type
杂志文章abstract::The mouse is widely used as system to study human genetic mechanisms. However, extensive rewiring of transcriptional regulatory networks often confounds translation of findings between human and mouse. Site-specific gain and loss of individual transcription factor binding sites (TFBS) has caused functional divergence ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky018
更新日期:2018-02-28 00:00:00
abstract::We have assessed the ability of nucleosomes to influence the formation of mammalian topoisomerase II-DNA complexes by mapping the sites of cleavage induced by four unrelated topoisomerase II inhibitors in naked versus nucleosome-reconstituted SV40 DNA. DNA fragments were reconstituted with histone octamers from HeLa c...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.15.4553
更新日期:1990-08-11 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::Existence of some extra-genetic (epigenetic) codes has been postulated since the discovery of the primary genetic code. Evident effects of histone post-translational modifications or DNA methylation over the efficiency and the regulation of DNA processes are supporting this postulation. EMdeCODE is an original algorit...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1214
更新日期:2013-02-01 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::The ORFDB (http://orf.invitrogen.com/) represents an ongoing effort at Invitrogen Corporation to integrate relevant scientific data with an evolving collection of human and mouse Open Reading Frame (ORF) clones (Ultimate ORF Clones). The ORFDB serves as a central data warehouse enabling researchers to search the ORF c...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh118
更新日期:2004-01-01 00:00:00
abstract::The early palindrome domain within the SV40 core origin of replication is essential for the initiation of replication. Studies with single point mutants in this region suggested that the early palindrome domain does not function as a cruciform structure, but may be involved in the initiation of SV40 DNA replication in...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:
更新日期:1989-11-25 00:00:00
abstract::Uracil-Specific Exision Reagent (USER) fusion is a recently developed technique that allows for assembly of multiple DNA fragments in a few simple steps. However, designing primers for USER fusion is both tedious and time consuming. Here, we present the Primer Help for USER (PHUSER) software, a novel tool for designin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr394
更新日期:2011-07-01 00:00:00
abstract::Molecules of single-stranded ribosomal RNA and double-stranded replicative form of phage f2 RNA (dsRNA) adopt a compact form in solutions, containing sufficiently high concentrations of salt (NaCl) and polymer (PEG). However, only in the cases of native dsRNA molecules the compact particles are characterized by a regu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/3.6.1533
更新日期:1976-06-01 00:00:00
abstract::TORQUE is a tool for cross-species querying of protein-protein interaction networks. It aims to answer the following question: given a set of proteins constituting a known complex or a pathway in one species, can a similar complex or pathway be found in the protein network of another species? To this end, Torque seeks...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp474
更新日期:2009-07-01 00:00:00
abstract::The interactions of self-complementary oligonucleotides with a group of metal-mediated DNA-binding drugs, including chromomycin A(3), mithramycin and the novel compound UK-1, were examined via electrospray ionization quadrupole ion trap mass spectrometry. Both chromomycin and mithramycin were shown to bind preferentia...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.21.e103
更新日期:2001-11-01 00:00:00
abstract::The archaeal and eukaryotic evolutionary domains diverged from each other approximately 2 billion years ago, but many of the core components of their transcriptional and translational machineries still display a readily recognizable degree of similarity in their primary structures. The F and P subunits present in arch...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.21.4299
更新日期:2000-11-01 00:00:00
abstract::A series of unusual folding regions (UFR) immediately 3' to the cleavage site of the outer membrane protein (OMP) and transmembrane protein (TMP) were detected in the envelope gene RNA of the human immunodeficiency virus (HIV-1, HIV-2) and simian immunodeficiency virus (SIV) by an extensive Monte Carlo simulation. The...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.6.1613
更新日期:1990-03-25 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::The template requirements for efficient adenovirus DNA replication were studied in vitro in a reconstituted system with cloned DNA fragments, containing the Ad2 origin region, as templates. Replication is enhanced by nuclear factor I, a cellular protein that binds specifically to the Ad2 origin. This stimulation is sh...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.13.4935
更新日期:1985-07-11 00:00:00
abstract::The role of uracil in genomic DNA has been recently re-evaluated. It is now widely accepted to be a physiologically important DNA element in diverse systems from specific phages to antibody maturation and Drosophila development. Further relevant investigations would largely benefit from a novel reliable and fast metho...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv977
更新日期:2016-02-18 00:00:00
abstract::Although the human alpha-globin and beta-globin genes are co-regulated in adult life, they achieve the same end by very different mechanisms. For example, a transfected beta-globin gene is expressed in an inducible manner in mouse erythroleukemia (MEL) cells while a transfected alpha-globin gene is constitutively expr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.2.342
更新日期:1996-01-15 00:00:00
abstract::Bovine mitochondrial (mt) phenylalanine tRNA (tRNA(Phe)), which lacks the 'conserved' GG and T psi YCG sequences, was efficiently purified by the selective hybridization method using a solid phase DNA probe. The entire nucleotide sequence of the tRNA, including modified nucleotides, was determined and its higher-order...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.3.347
更新日期:1994-02-11 00:00:00
abstract::We describe a versatile and extensible integrated bioinformatics toolkit for the analysis of biological sequences over the Internet. The web portal offers convenient interactive access to a growing pool of chainable bioinformatics software tools and databases that are centrally installed and maintained by the RZG. Cur...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl254
更新日期:2006-07-01 00:00:00
abstract::Genomic studies have indicated that certain bacterial lineages such as the Bacteroidetes lack Shine-Dalgarno (SD) sequences, and yet with few exceptions ribosomes of these organisms carry the canonical anti-SD (ASD) sequence. Here, we show that ribosomes purified from Flavobacterium johnsoniae, a representative of the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa1195
更新日期:2021-01-11 00:00:00
abstract::DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic and cell-non-autonomous pathways. Studying the consequences of DSBs in higher organisms has, howeve...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1482
更新日期:2016-04-20 00:00:00
abstract::Type IIS restriction endonuclease BtsCI (GGATG 2/0) is a neoschizomer of FokI (GGATG 9/13) and cleaves closer to the recognition sequence. Although M.BtsCI shows 62% amino acid sequence identity to M.FokI, BtsCI and FokI restriction endonucleases do not share significant amino acid sequence similarity. BtsCI belongs t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp1092
更新日期:2010-03-01 00:00:00
abstract::Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw095
更新日期:2016-06-02 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::A novel method to measure mRNA levels has been developed by combining the detection capabilities of RNase protection (RPA) with the quantification advantages of scintillation proximity assay (SPA) technology. Sample processing is reduced to the addition of a single reagent post RNase digestion. As a model system, the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.14.2947
更新日期:1997-07-15 00:00:00
abstract::The Bacillus cereus genome possesses three type IA topoisomerase genes. These genes, encoding DNA topoisomerase I and IIIalpha (bcTopo I, bcTopo IIIalpha), have been cloned into T7 RNA polymerase-regulated plasmid expression vectors and the enzymes have been overexpressed, purified and characterized. The proteins exhi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki846
更新日期:2005-09-28 00:00:00
abstract::The conformations of supercoiled (sc) DNA and linear DNA bound to polylysine (PL)-coated mica were investigated by scanning force microscopy (SFM) in solution. From the polymer statistical analysis of linear DNA, we could distinguish between re-arrangements or trapping of the DNA on the surface. Conditions of re-arran...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gng137
更新日期:2003-11-15 00:00:00
abstract::Pyrimidine adducts in cellular DNA arise from modification of the pyrimidine 5,6-double bond by oxidation, reduction or hydration. The biological outcome includes increased mutation rate and potential lethality. A major DNA N:-glycosylase responsible for the excision of modified pyrimidine bases is the base excision r...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.3.604
更新日期:2001-02-01 00:00:00
abstract::We report a novel system for efficient and specific targeted delivery of large nucleic acids to and into cells. Plasmid DNA and core histones were assembled to chromatin by salt gradient dialysis and subsequently connected to bispecific antibody derivatives (bsAbs) via a nucleic acid binding peptide bridge. The result...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz137
更新日期:2019-06-04 00:00:00
abstract::The 3'-untranslated region (UTR) of tobacco mosaic virus (TMV), which terminates in a tRNA-like structure, functionally substitutes for a poly(A) tail in both plant and animal cells. The addition of the TMV 3'-UTR to chimeric mRNA constructs increases their expression up to 100-fold, increasing both translational effi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.18.5031
更新日期:1991-09-25 00:00:00