Abstract:
:G-quadruplexes (G4s) are stable secondary structures that can lead to the stalling of replication forks and cause genomic instability. Pif1 is a 5' to 3' helicase, localized to both the mitochondria and nucleus that can unwind G4s in vitro and prevent fork stalling at G4 forming sequences in vivo. Using in vitro primer extension assays, we show that both G4s and stable hairpins form barriers to nuclear and mitochondrial DNA polymerases δ and γ, respectively. However, while single-stranded DNA binding proteins (SSBs) readily promote replication through hairpins, SSBs are only effective in promoting replication through weak G4s. Using a series of G4s with increasing stabilities, we reveal a threshold above which G4 through-replication is inhibited even with SSBs present, and Pif1 helicase is required. Because Pif1 moves along the template strand with a 5'-3'-directionality, head-on collisions between Pif1 and polymerase δ or γ result in the stimulation of their 3'-exonuclease activity. Both nuclear RPA and mitochondrial SSB play a protective role during DNA replication by preventing excessive DNA degradation caused by the helicase-polymerase conflict.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Sparks MA,Singh SP,Burgers PM,Galletto Rdoi
10.1093/nar/gkz608subject
Has Abstractpub_date
2019-09-19 00:00:00pages
8595-8605issue
16eissn
0305-1048issn
1362-4962pii
5538013journal_volume
47pub_type
杂志文章abstract::Pseudomonas aeruginosa is an opportunistic pathogen with a relatively large genome, and has been shown to routinely lose genomic fragments during environmental selection. However, the underlying molecular mechanisms that promote chromosomal deletion are still poorly understood. In a recent study, we showed that by del...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky160
更新日期:2018-05-18 00:00:00
abstract::Understanding the normal state of human tissue transcriptome profiles is essential for recognizing tissue disease states and identifying disease markers. Recently, the Human Protein Atlas and the FANTOM5 consortium have each published extensive transcriptome data for human samples using Illumina-sequenced RNA-Seq and ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv608
更新日期:2015-08-18 00:00:00
abstract::We have studied the ability of the wt1 tumor suppressor gene product to repress different classes of activation domains previously shown to stimulate the initiation and elongation steps of RNA polymerase II transcription in vivo. Repression assays revealed that WT1 represses all three classes of activation domains: Sp...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.14.2889
更新日期:1999-07-15 00:00:00
abstract::2'-O-Aminooxymethyl ribonucleosides are prepared from their 3',5'-disilylated 2'-O-phthalimidooxymethyl derivatives by treatment with NH(4)F in MeOH. The reaction of these novel ribonucleosides with 1-pyrenecarboxaldehyde results in the efficient formation of stable and yet reversible ribonucleoside 2'-conjugates in y...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr896
更新日期:2012-03-01 00:00:00
abstract::The variation of the proton chemical shifts due to the formation intermolecular hydrogen bonds is computed for a number of complexes which can be formed between the bases of the nucleic acids. The shifts expected for the isolated base pairs, in particular for the G-N1 H, T(or U)-N3H protons and the protons of the amin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.1.99
更新日期:1977-01-01 00:00:00
abstract::The human gene for plasminogen activator inhibitor type-1 (PAI-1) has been isolated and its promoter region characterized. PAI-1 regulation by glucocorticoids, transforming growth factor-beta (TGF-beta) and the phorbol ester PMA is shown to be exerted at the promoter level. A fragment spanning 805 nucleotides of the 5...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.7.2805
更新日期:1988-04-11 00:00:00
abstract::The Functional Single Nucleotide Polymorphism (F-SNP) database integrates information obtained from 16 bioinformatics tools and databases about the functional effects of SNPs. These effects are predicted and indicated at the splicing, transcriptional, translational and post-translational level. As such, the database h...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm904
更新日期:2008-01-01 00:00:00
abstract::Mutations of the KRAS proto-oncogene are associated with several tumor types, which is why it is being considered as a target for anti-cancer drug development. The human KRAS promoter contains a nuclease hypersensitive element (NHE), which can bind to nuclear proteins and is believed to form G-quadruplex structures. P...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1359
更新日期:2016-01-29 00:00:00
abstract::NRPS-PKS is web-based software for analysing large multi-enzymatic, multi-domain megasynthases that are involved in the biosynthesis of pharmaceutically important natural products such as cyclosporin, rifamycin and erythromycin. NRPS-PKS has been developed based on a comprehensive analysis of the sequence and structur...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh359
更新日期:2004-07-01 00:00:00
abstract::Non-radioactive nucleic acid hybridization probes have been constructed in which the reporter group is long chain biotin chemically linked to a basic macromolecule (histone H1, cytochrome C or polyethyleneimine). The modified basic macromolecule which carries many biotin residues can, in turn, be covalently linked to ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.24.9965
更新日期:1986-12-22 00:00:00
abstract::The herpes simplex virus protein VP16 interacts with cellular factors, including the protein Oct-1, to activate viral immediate early (IE) gene transcription. We have reproduced this effect by addition of purified, full-length VP16 and the DNA-binding 'POU' domain of Oct-1 (Oct-1/POU) to a HeLa cell in vitro transcrip...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.24.5570
更新日期:1993-12-11 00:00:00
abstract::To explain the activation of transcription by a remote enhancer, two models are most often considered, namely looping and scanning. A scanning model, also referred to as 'polymerase entry site' model predicts that for two adjacent promoters the one proximal to an enhancer would be preferentially activated. Preferentia...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.22.8931
更新日期:1989-11-25 00:00:00
abstract::We describe the further development of a widely used package of DNA/protein sequence analysis programs (1). Important revisions have been made based on user experience, and new features, multi-user capability, and a set of large scale homology programs have been added. The programs are very user friendly, economical o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.1part2.643
更新日期:1984-01-11 00:00:00
abstract::Plant orthologs of the yeast sucrose non-fermenting (Snf1) kinase and mammalian AMP-activated protein kinase (AMPK) represent an emerging class of important regulators of metabolic and stress signalling. The catalytic alpha-subunits of plant Snf1-related kinases (SnRKs) interact in the yeast two-hybrid system with dif...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.17.3685
更新日期:2001-09-01 00:00:00
abstract::We describe a cell-free chromatin assembly system derived from the yeast Saccharomyces cerevisiae, which efficiently packages DNA into minichromosomes in a reaction dependent on exogenous core histones and an ATP-regenerating system. Both supercoiled and relaxed plasmid DNA serve as templates for nucleosomal loading i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gnh107
更新日期:2004-07-28 00:00:00
abstract::Population-scale sequencing is increasingly uncovering large numbers of rare single-nucleotide variants (SNVs) in coding regions of the genome. The rarity of these variants makes it challenging to evaluate their deleteriousness with conventional phenotype-genotype associations. Protein structures provide a way of addr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw927
更新日期:2016-12-01 00:00:00
abstract::Nuclear extracts prepared from growth hormone-secreting (GC) and prolactin-secreting (235-1) rat anterior pituitary cell lines were compared for their ability to bind to the DNA sequences conferring tissue-specificity to the expression of the rat growth hormone (rGH) gene promoter. Cell-specific differences in the int...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.17.5235
更新日期:1990-09-11 00:00:00
abstract::The DEAH-box NTPase Prp43 disassembles spliceosomes in co-operation with the cofactors Ntr1/Spp382 and Ntr2, forming the NTR complex. How Prp43 is regulated by its cofactors to discard selectively only intron-lariat spliceosomes (ILS) and defective spliceosomes and to prevent disassembly of earlier and properly assemb...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1225
更新日期:2017-04-20 00:00:00
abstract::3'-O-(5'-phosphoryldeoxycytidyl) phosphorothioate and fluorescent 3'-O-(5'-phosphoryldeoxycytidyl) S-bimane phosphorothioate can be ligated to tRNA by T4 RNA ligase. They are also efficient donors for the enzymatic ligation to oligodeoxynucleotides bearing a 3'-cytidine terminus. Cytidine 3',5'-bisphosphate is also a ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.4.1791
更新日期:1984-02-24 00:00:00
abstract::Furvina®, also denominated G1 (MW 297), is a synthetic nitrovinylfuran [2-bromo-5-(2-bromo-2-nitrovinyl)-furan] antibiotic with a broad antimicrobial spectrum. An ointment (Dermofural®) containing G1 as the only active principle is currently marketed in Cuba and successfully used to treat dermatological infections. He...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks822
更新日期:2012-11-01 00:00:00
abstract::MolProbity is a general-purpose web server offering quality validation for 3D structures of proteins, nucleic acids and complexes. It provides detailed all-atom contact analysis of any steric problems within the molecules as well as updated dihedral-angle diagnostics, and it can calculate and display the H-bond and va...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm216
更新日期:2007-07-01 00:00:00
abstract::The selective and potent inhibition of mitochondrial translation in Saccharomyces cerevisiae by pentamidine suggests a novel antimicrobial action for this drug. Electrophoresis mobility shift assay, T1 ribonuclease footprinting, hydroxyl radical footprinting and isothermal titration calorimetry collectively demonstrat...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm1180
更新日期:2008-03-01 00:00:00
abstract::Bleomycin B(2)(BLM) in the presence of iron [Fe(II)] and O(2)catalyzes single-stranded (ss) and double-stranded (ds) cleavage of DNA. Electrospray ionization ion trap mass spectrometry was used to monitor these cleavage processes. Two duplex oligonucleotides containing an ethylene oxide tether between both strands wer...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.9.1978
更新日期:2000-05-01 00:00:00
abstract::DNA damage-induced cell cycle checkpoints serve as surveillance mechanisms to maintain genomic stability, and are regulated by ATM/ATR-mediated signaling pathways that are conserved from yeast to humans. Trypanosoma brucei, an early divergent microbial eukaryote, lacks key components of the conventional DNA damage-ind...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz476
更新日期:2019-09-05 00:00:00
abstract::The rat alpha- and bovine alpha s1-casein genes have been isolated and their 5' sequences determined. The rat alpha-, beta-, gamma- and bovine alpha s1-casein genes contain similar 5' exon arrangements in which the 5' noncoding, signal peptide and casein kinase phosphorylation sequences are each encoded by separate ex...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.4.1883
更新日期:1986-02-25 00:00:00
abstract::The restriction endonuclease (R.BsuFI) of Bacillus subtilis recognizes the target DNA sequence 5' CCGG. The R.BsuFI gene was found in close proximity to the cognate M.BsuFI gene, which had previously been characterized (1). Cloning of the R.BsuFI gene in E.coli was only possible with the M.BsuFI Mtase gene present on ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.23.6457
更新日期:1991-12-11 00:00:00
abstract::The design and synthesis of metal complexes that can specifically target DNA secondary structure has attracted considerable attention. Chiral metallosupramolecular complexes (e.g. helicates) in particular display unique DNA-binding behavior, however until recently few examples which are both water-compatible and enant...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx244
更新日期:2017-05-19 00:00:00
abstract::The transcription activator-like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR) associated protein (Cas9) utlilize distinct molecular mechanisms in targeting site recognition. The two proteins can be modified to carry additional functional domains to regulate exp...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku836
更新日期:2014-11-10 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::Fibroblast growth factor receptor 3 (FGFR3) plays an important role in cartilage development. Although upregulation of FGFR3 expression in response to bone morphogenetic protein-2 (BMP-2) has been reported, the molecular mechanisms remain unknown. In this study, we used in vivo approaches to characterize BMP-2-induced...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp261
更新日期:2009-07-01 00:00:00