Abstract：
:Poly (ADP-ribose) polymerase 1 (PARP1) has emerged as an attractive target for cancer therapy due to its key role in DNA repair processes. Inhibition of PARP1 in BRCA-mutated cancers has been observed to be clinically beneficial. Recent genome-mapping experiments have identified a non-canonical G-quadruplex-forming sequence containing bulges within the PARP1 promoter. Structural features, like bulges, provide opportunities for selective chemical targeting of the non-canonical G-quadruplex structure within the PARP1 promoter, which could serve as an alternative therapeutic approach for the regulation of PARP1 expression. Here we report the G-quadruplex structure formed by a 23-nucleotide G-rich sequence in the PARP1 promoter. Our study revealed a three-layered intramolecular (3+1) hybrid G-quadruplex scaffold, in which three strands are oriented in one direction and the fourth in the opposite direction. This structure exhibits unique structural features such as an adenine bulge and a G·G·T base triple capping structure formed between the central edgewise loop, propeller loop and 5' flanking terminal. Given the highly important role of PARP1 in DNA repair and cancer intervention, this structure presents an attractive opportunity to explore the therapeutic potential of PARP1 inhibition via G-quadruplex DNA targeting.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Sengar A,Vandana JJ,Chambers VS,Di Antonio M,Winnerdy FR,Balasubramanian S,Phan ATdoi
10.1093/nar/gky1179subject
Has Abstractpub_date
2019-02-20 00:00:00pages
1564-1572issue
3eissn
0305-1048issn
1362-4962pii
5248355journal_volume
47pub_type
杂志文章abstract：:Short repetitive DNA sequences are believed to be one of the primordial genetic elements that served as a source of complex large DNA found in the genome of modern organisms. However, the mechanism of its expansion (increase in repeat number) during the course of evolution is unclear. We demonstrate that the DNA polym...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/28.20.3999
更新日期：2000-10-15 00:00:00
abstract：:The surface accessibility of macromolecules plays a key role in modulating molecular recognition events. RNA is a complex and dynamic molecule involved in many aspects of gene expression. However, there are few experimental methods available to measure the accessible surface of RNA. Here, we investigate the accessible...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkm1062
更新日期：2008-03-01 00:00:00
abstract：:Adenosine-to-inosine (A-to-I) RNA editing is a common post transcriptional modification. It has a critical role in protecting against false activation of innate immunity by endogenous double stranded RNAs and has been associated with various regulatory processes and diseases such as autoimmune and cardiovascular disea...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkaa305
更新日期：2020-06-19 00:00:00
abstract：:Base excision repair (BER), which is initiated by DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. The NTHL1 glycosylase, which excises DNA base damage caused by reactive oxygen species, is thought to be a tumor suppressor. However, in addition to NTHL1 loss-of-function...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gky162
更新日期：2018-05-18 00:00:00
abstract：:We have compared the properties of the poly(rA).oligo(dT) complex with those of the poly(rU).oligo(dA)n complex. Three main differences were found. First, poly(rA) and oligo(dT)n do not form a complex in concentrations of CsCl exceeding 2 M because the poly(rA) is insoluble in high salt. If the complex is made in low ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/3.4.1013
更新日期：1976-04-01 00:00:00
abstract：:The sequence of the 3'-terminal 180 and 140 nucleotides of RNAs 2 and 3, respectively, of tobacco streak virus (TSV) was deduced by reverse transcription in the presence of a specific primer and chain terminators. Homology between the two RNAs was found to be restricted to a 3-terminal region of about 45 nucleotides. ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/8.15.3307
更新日期：1980-08-11 00:00:00
abstract：:This laboratory has established in previous studies that Pmel 17, a gene expressed specifically in melanocytes, maps near the silver coat color locus (si/si) on mouse chromosome 10. In the current study, we have focused on determining whether or not the si allele carries a mutation in Pmel 17. Pmel 17 cDNA clones, iso...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/23.1.154
更新日期：1995-01-11 00:00:00
abstract：:GGRNA (http://GGRNA.dbcls.jp/) is a Google-like, ultrafast search engine for genes and transcripts. The web server accepts arbitrary words and phrases, such as gene names, IDs, gene descriptions, annotations of gene and even nucleotide/amino acid sequences through one simple search box, and quickly returns relevant Re...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gks448
更新日期：2012-07-01 00:00:00
abstract：:We have developed efficient methods for creating artificial transposons and inserting these transposons into plasmid targets in vitro, primarily for the purpose of DNA mapping and sequencing. A novel plasmid has been engineered to convert virtually any DNA sequence, or combination of sequences, into an artificial tran...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/22.18.3765
更新日期：1994-09-11 00:00:00
abstract：:The high-throughput sequencing of nuclease-protected mRNA fragments bound to ribosomes, a technique known as ribosome profiling, quantifies the relative frequencies with which different regions of transcripts are translated. This technique has revealed novel translation initiation sites with unprecedented scope and ha...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv200
更新日期：2015-04-20 00:00:00
abstract：:The agents daunomycin, ethidium bromide, distamycin A and cytochrome c inhibit DNA dependent DNA polymerase I (E. coli) reaction competitively to DNA. The influence of these template inactivators on the binding of DNA polymerase to native as well as denatured DNA has been determined by affinity chromatography. Cytochr...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/1.1.63
更新日期：1974-01-01 00:00:00
abstract：:A human telomere ends in a single-stranded 3' tail, composed of repeats of T2AG3. G-quadruplexes (GQs) formed from four consecutive repeats have been shown to possess high-structural and mechanical diversity. In principle, a GQ can form from any four repeats that are not necessarily consecutive. To understand the dyna...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkz906
更新日期：2019-12-02 00:00:00
abstract：:The sequences coding for DNA[cytosine-N4]methyltransferases MvaI (from Micrococcus varians RFL19) and Cfr9I (from Citrobacter freundii RFL9) have been determined. The predicted methylases are proteins of 454 and 300 amino acids, respectively. Primary structure comparison of M.Cfr9I and another m4C-forming methylase, M...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/17.23.9823
更新日期：1989-12-11 00:00:00
abstract：:A number of different protecting groups were compared with respect to their usefulness for protection of 2'-hydroxyl functions during synthesis of oligoribonucleotides using the H-phosphonate approach. The comparison was between the t-butyldimethylsilyl (t-BDMSi), the o-chlorobenzoyl (o-CIBz), the tetrahydropyranyl (T...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/22.1.94
更新日期：1994-01-11 00:00:00
abstract：:This review presents detailed information about the structure of triplet repeat RNA and addresses the simple sequence repeats of normal and expanded lengths in the context of the physiological and pathogenic roles played in human cells. First, we discuss the occurrence and frequency of various trinucleotide repeats in...
journal_title：Nucleic acids research
pub_type： 杂志文章,评审
doi：10.1093/nar/gkr729
更新日期：2012-01-01 00:00:00
abstract：:Mature chicken erythrocyte polynucleosomes which are soluble at physiological ionic strength are enriched in beta-globin DNA sequences. Vitellogenin chromatin, which is not expressed in this tissue, is found in aggregation prone, salt insoluble chromatin. There is a direct correlation between the size of soluble fragm...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/15.3.1081
更新日期：1987-02-11 00:00:00
abstract：:Restriction endonucleases are highly specific in recognizing the particular DNA sequence they act on. However, their activity is affected by sequence context, enzyme concentration and buffer composition. Changes in these factors may lead to either ineffective cleavage at the cognate restriction site or relaxed specifi...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt257
更新日期：2013-06-01 00:00:00
abstract：:Inspection of the structure of the C-terminal domain of ribosomal protein L7/L12 (1) reveals a helix-turn-helix motif similar to the one found in many DNA-binding regulatory proteins (2-5). The 19 alpha-carbon atoms of the L7/L12 alpha-helices superimpose on the DNA binding helices of CAP and cro with root-mean-square...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/17.10.3757
更新日期：1989-05-25 00:00:00
abstract：:The human RAD54B protein is a paralog of the RAD54 protein, which plays important roles in homologous recombination. RAD54B contains an N-terminal region outside the SWI2/SNF2 domain that shares less conservation with the corresponding region in RAD54. The biochemical roles of this region of RAD54B are not known, alth...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkn516
更新日期：2008-10-01 00:00:00
abstract：:Four phage clones which hybridize with U1 small nuclear RNA were obtained from a rat gene library. Two clones contain a presumed pseudogene. A third clone includes two gene candidates that are co-linear with the rat U1-RNA, 3.6kb apart and in the opposite orientation. The two genes are surrounded by identical sequence...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/11.6.1791
更新日期：1983-03-25 00:00:00
abstract：:Specific targeting of protein–nucleic acid interactions is an area of current interest, for example, in the regulation of gene-expression. Most transcription factor proteins bind in the DNA major groove; however, we are interested in an approach using small molecules to target the minor groove to control expression by...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkw1232
更新日期：2017-02-17 00:00:00
abstract：:Post-translational modifications contribute to the spliceosome dynamics by facilitating the physical rearrangements of the spliceosome. Here, we report USP15, a deubiquitinating enzyme, as a regulator of protein-protein interactions for the spliceosome dynamics. We show that PRP31, a component of U4 snRNP, is modified...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkw1365
更新日期：2017-05-05 00:00:00
abstract：:Bacillus stearothermophilus large ribosomal subunits were reconstituted in the presence of 5S rRNAs from different origins and tested for their biological activities. The results obtained have shown that eubacterial and archaebacterial 5S rRNAs can easily substitute for B. stearothermophilus 5S rRNA in the reconstitut...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/16.8.3511
更新日期：1988-04-25 00:00:00
abstract：:We took advantage of the unusual genomic organization of the ciliate Oxytricha trifallax to screen for eukaryotic non-coding RNA (ncRNA) genes. Ciliates have two types of nuclei: a germ line micronucleus that is usually transcriptionally inactive, and a somatic macronucleus that contains a reduced, fragmented and rear...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkr501
更新日期：2011-09-01 00:00:00
abstract：:WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkz920
更新日期：2020-01-08 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：:The interaction of antibodies directed toward N6-(delta2-isopentenyl)adenosine, i6Ado, or its nucleotide with related bases, nucleosides, nucleotides and purified tRNAs is described. The selectivity of the antibody preparation was tested in inhibition experiments utilizing a sensitive radioimmunoassay to quantitate th...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/5.9.3439
更新日期：1978-09-01 00:00:00
abstract：:The essential splicing factor Prp24 contains four RNA Recognition Motif (RRM) domains, and functions to anneal U6 and U4 RNAs during spliceosome assembly. Here, we report the structure and characterization of the C-terminal RRM4. This domain adopts a novel non-canonical RRM fold with two additional flanking α-helices ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkr455
更新日期：2011-09-01 00:00:00
abstract：:The GeneSpeed database (http://genespeed.uchsc.edu/) is an online database and resource tool facilitating the detailed study of protein domain homology in the transcriptomes of Homo sapiens, Mus musculus, Drosophila melanogaster and Caenorhabditis elegans. The population schema for the GeneSpeed database takes advanta...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkl990
更新日期：2007-01-01 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
