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：:A UCSD Pascal program was developed which can analyze nucleic acid dot matrices of up to 9500 X 9500 in size on the Apple II computer. Although matrices of such size consume large amounts of computer memory, this program minimizes these problems by analyzing only small strips of the matrix at a time, and then transfer...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/12.1part2.767
更新日期：1984-01-11 00:00:00
abstract：:The Restriction-modification system AhdI contains two convergent transcription units, one with genes encoding methyltransferase subunits M and S and another with genes encoding the controller (C) protein and the restriction endonuclease (R). We show that AhdI transcription is controlled by two independent regulatory l...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkm1116
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abstract：:A dot hybridization method is presented for rapidly determining the relative concentrations of nucleic acids in a mixture, as well as the extent of sequence homology between related RNA or DNA species. ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/7.6.1541
更新日期：1979-11-24 00:00:00
abstract：:The plastid psbA promoter of tobacco was used with the aim to construct plastid specific marker genes. Upon transfer to the tobacco nuclear genome the plastid promoter fragment appeared to specify a messenger RNA. Placed 5' to the bar or nptII coding sequences the level of expression is sufficient to obtain a selectab...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/17.1.19
更新日期：1989-01-11 00:00:00
abstract：:An updated list of DNA sequences cloned from the human genome over the past year (1991) is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic probes comprising both gene and pseudogene sequences. ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/20.suppl.2181
更新日期：1992-05-11 00:00:00
abstract：:Patients with Alzheimer's disease (AD) exhibit higher levels of 8-oxo-guanine (8-oxoG) DNA lesions in their brain, suggesting a reduced or defective 8-oxoG repair. To test this hypothesis, this study investigated 14 AD patients and 10 age-matched controls for mutations of the major 8-oxoG removal gene OGG1. Whereas no...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkm189
更新日期：2007-01-01 00:00:00
abstract：:VIDA is a new virus database that organizes open reading frames (ORFs) from partial and complete genomic sequences from animal viruses. Currently VIDA includes all sequences from GenBank for Herpesviridae, Coronaviridae and Arteriviridae. The ORFs are organized into homologous protein families, which are identified on...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/29.1.133
更新日期：2001-01-01 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/19.3.461
更新日期：1991-02-11 00:00:00
abstract：:Riboswitches are RNA-based regulatory devices that mediate ligand-dependent control of gene expression. However, there has been limited success in rationally designing riboswitches. Moreover, most previous riboswitches are confined to a particular gene and only perform one-way regulation. Here, we used a library scree...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkr609
更新日期：2011-10-01 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/23.6.885
更新日期：1995-03-25 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/14.14.5885
更新日期：1986-07-25 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/26.11.2580
更新日期：1998-06-01 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/20.15.3911
更新日期：1992-08-11 00:00:00
abstract：:Gene transfer and expression in eukaryotes is often limited by a number of stably maintained gene copies and by epigenetic silencing effects. Silencing may be limited by the use of epigenetic regulatory sequences such as matrix attachment regions (MAR). Here, we show that successive transfections of MAR-containing vec...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkr436
更新日期：2011-08-01 00:00:00
abstract：:The promoter of the human BCR gene, regulating the transcription of the chimeric BCR/ABL mRNA in leukemia, has been isolated and characterized. A region of 1.1 kb immediately 5' to the transcription start site was analyzed in detail by sequencing, DNase 1 footprinting, gel retardation and functional studies. These exp...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/18.23.7119
更新日期：1990-12-11 00:00:00
abstract：:TIGRFAMs is a collection of protein family definitions built to aid in high-throughput annotation of specific protein functions. Each family is based on a hidden Markov model (HMM), where both cutoff scores and membership in the seed alignment are chosen so that the HMMs can classify numerous proteins according to the...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkl1043
更新日期：2007-01-01 00:00:00
abstract：:T1DBase (http://www.t1dbase.org) is web platform, which supports the type 1 diabetes (T1D) community. It integrates genetic, genomic and expression data relevant to T1D research across mouse, rat and human and presents this to the user as a set of web pages and tools. This update describes the incorporation of new dat...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkq912
更新日期：2011-01-01 00:00:00
abstract：:Chromatin boundaries regulate gene expression by modulating enhancer-promoter interactions and insulating transcriptional influences from organized chromatin. However, mechanistic distinctions between these two aspects of boundary function are not well understood. Here we show that SF1, a chromatin boundary located in...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkp362
更新日期：2009-07-01 00:00:00
abstract：:Essential genes are genes that are indispensable to support cellular life. These genes constitute a minimal gene set required for a living cell. We have constructed a Database of Essential Genes (DEG), which contains all the essential genes that are currently available. The functions encoded by essential genes are con...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkh024
更新日期：2004-01-01 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
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更新日期：2011-11-01 00:00:00
abstract：:Fluorogenic RNAs that are based on the complex formed by 3,5-difluoro-4-hydroxybenzylidene imidazolinone (DFHBI) derivatives and the RNA aptamer named Spinach were used to engineer a new generation of in vitro and in vivo sensors for bioanalytics. With the resolved crystal structure of the RNA/small molecule complex, ...
journal_title：Nucleic acids research
pub_type： 杂志文章
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journal_title：Nucleic acids research
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更新日期：2019-01-08 00:00:00
abstract：:Highly repetitive Hind III restriction fragments of 0.72-0.76 KBP from total Xenopus laevis genomic DNA are organized in a tandem like arrangement. Cloning of these fragments in pBR 322 with subsequent restriction site mapping and nucleotide sequence analysis of some selected clones showed two different types of seque...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/11.20.6997
更新日期：1983-10-25 00:00:00
abstract：:The chromatin-remodelling complex B-WICH, comprised of William syndrome transcription factor, the ATPase SNF2h and nuclear myosin, specifically activates RNA polymerase III transcription of the 5S rRNA and 7SL genes. However, the underlying mechanism is unknown. Using high-resolution MN walking we demonstrate here tha...
journal_title：Nucleic acids research
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更新日期：2015-05-19 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
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更新日期：2018-04-20 00:00:00
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journal_title：Nucleic acids research
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更新日期：2009-07-01 00:00:00
abstract：:Some human cancers maintain their telomeres using the alternative lengthening of telomeres (ALT) mechanism; a process thought to involve recombination. Different types of recombinational telomere elongation pathways have been identified in yeasts. In senescing yeast telomerase deletion (ter1-Delta) mutants with very s...
journal_title：Nucleic acids research
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更新日期：2010-01-01 00:00:00
abstract：:The thymine analog 5-chlorouridine, first reported in the 1950s as anti-tumor agent, is known as an effective mutagen, clastogen and toxicant as well as an effective inducer of sister-chromatid exchange. Recently, the first microorganism with a chemically different genome was reported; the selected Escherichia coli st...
journal_title：Nucleic acids research
pub_type： 杂志文章
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更新日期：2013-02-01 00:00:00
abstract：:Adaptive Laboratory Evolution (ALE) has emerged as an experimental approach to discover causal mutations that confer desired phenotypic functions. ALE not only represents a controllable experimental approach to systematically discover genotype-phenotype relationships, but also allows for the revelation of the series o...
journal_title：Nucleic acids research
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更新日期：2019-01-08 00:00:00
abstract：:A growing number of whole genome sequencing projects, in combination with development of phylogenetic methods for reconstructing gene evolution, have provided us with a window into genomes that existed millions, and even billions, of years ago. Ancestral Genomes (http://ancestralgenomes.org) is a resource for comprehe...
journal_title：Nucleic acids research
pub_type： 杂志文章
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更新日期：2019-01-08 00:00:00
