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Genetic interactions of G-quadruplexes in humans.

eLife | 2019

G-quadruplexes (G4) are alternative nucleic acid structures involved in transcription, translation and replication. Aberrant G4 formation and stabilisation is linked to genome instability and cancer. G4 ligand treatment disrupts key biological processes leading to cell death. To discover genes and pathways involved with G4s and gain mechanistic insights into G4 biology, we present the first unbiased genome-wide study to systematically identify human genes that promote cell death when silenced by shRNA in the presence of G4-stabilising small molecules. Many novel genetic vulnerabilities were revealed opening up new therapeutic possibilities in cancer, which we exemplified by an orthogonal pharmacological inhibition approach that phenocopies gene silencing. We find that targeting the WEE1 cell cycle kinase or USP1 deubiquitinase in combination with G4 ligand treatment enhances cell killing. We also identify new genes and pathways regulating or interacting with G4s and demonstrate that the DDX42 DEAD-box helicase is a newly discovered G4-binding protein.

Pubmed ID: 31287417 RIS Download

Associated grants

  • Agency: Royal Society, International
    Id: RP130039
  • Agency: Wellcome, International
    Id: 209441/z/17/z
  • Agency: Pew Charitable Trusts, International
    Id: 00028354
  • Agency: Cancer Research UK, United Kingdom
    Id: C14303/A17197
  • Agency: Cancer Research UK, United Kingdom
    Id: C9681/A18618
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Cancer Research UK, United Kingdom
    Id: A21143

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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COSMIC - Catalogue Of Somatic Mutations In Cancer (tool)

RRID:SCR_002260

Database to store and display somatic mutation information and related details and contains information relating to human cancers. The mutation data and associated information is extracted from the primary literature. In order to provide a consistent view of the data a histology and tissue ontology has been created and all mutations are mapped to a single version of each gene. The data can be queried by tissue, histology or gene and displayed as a graph, as a table or exported in various formats.
Some key features of COSMIC are:
* Contains information on publications, samples and mutations. Includes samples which have been found to be negative for mutations during screening therefore enabling frequency data to be calculated for mutations in different genes in different cancer types.
* Samples entered include benign neoplasms and other benign proliferations, in situ and invasive tumours, recurrences, metastases and cancer cell lines.

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UniProt (tool)

RRID:SCR_002380

Collection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.

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GitHub (tool)

RRID:SCR_002630

A web-based hosting service for software development projects that use the Git revision control system offering powerful collaboration, code review, and code management. It offers both paid plans for private repositories, and free accounts for open source projects. Large or small, every repository comes with the same powerful tools. These tools are open to the community for public projects and secure for private projects. Features include: * Integrated issue tracking * Collaborative code review * Easily manage teams within organizations * Text entry with understated power * A growing list of programming languages and data formats * On the desktop and in your pocket - Android app and mobile web views let you keep track of your projects on the go.

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ArrayExpress (tool)

RRID:SCR_002964

International functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.

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PubMed Central (tool)

RRID:SCR_004166

Collection of full text archive of biomedical and life sciences journal literature at U.S. National Institutes of Health National Library of Medicine (NIH/NLM). With PubMed Central, NCBI is taking lead in preserving and maintaining open access to electronic literature. Value of PubMed Central, in addition to its role as an archive, lies in what can be done when data from diverse sources is stored in common format in single repository. All articles in PMC are free (sometimes on a delayed basis). Some journals go beyond free, to Open Access.

View all literature mentions

UniProtKB (tool)

RRID:SCR_004426

Central repository for collection of functional information on proteins, with accurate and consistent annotation. In addition to capturing core data mandatory for each UniProtKB entry (mainly, the amino acid sequence, protein name or description, taxonomic data and citation information), as much annotation information as possible is added. This includes widely accepted biological ontologies, classifications and cross-references, and experimental and computational data. The UniProt Knowledgebase consists of two sections, UniProtKB/Swiss-Prot and UniProtKB/TrEMBL. UniProtKB/Swiss-Prot (reviewed) is a high quality manually annotated and non-redundant protein sequence database which brings together experimental results, computed features, and scientific conclusions. UniProtKB/TrEMBL (unreviewed) contains protein sequences associated with computationally generated annotation and large-scale functional characterization that await full manual annotation. Users may browse by taxonomy, keyword, gene ontology, enzyme class or pathway.

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MeSH (tool)

RRID:SCR_004750

A controlled vocabulary thesaurus that consists of sets of terms naming descriptors in a hierarchical structure that permits searching at various levels of specificity. MeSH, in machine-readable form, is provided at no charge via electronic means. MeSH descriptors are arranged in both an alphabetic and a hierarchical structure. At the most general level of the hierarchical structure are very broad headings such as Anatomy or Mental Disorders. More specific headings are found at more narrow levels of the twelve-level hierarchy, such as Ankle and Conduct Disorder. There are 27,149 descriptors in 2014 MeSH. There are also over 218,000 entry terms that assist in finding the most appropriate MeSH Heading, for example, Vitamin C is an entry term to Ascorbic Acid. In addition to these headings, there are more than 219,000 headings called Supplementary Concept Records (formerly Supplementary Chemical Records) within a separate thesaurus. The MeSH thesaurus is used by NLM for indexing articles from 5,400 of the world''''s leading biomedical journals for the MEDLINE/PubMED database. It is also used for the NLM-produced database that includes cataloging of books, documents, and audiovisuals acquired by the Library. Each bibliographic reference is associated with a set of MeSH terms that describe the content of the item. Similarly, search queries use MeSH vocabulary to find items on a desired topic.

View all literature mentions

PubMed (tool)

RRID:SCR_004846

Public bibliographic database that provides access to citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. PubMed citations and abstracts include fields of biomedicine and health, covering portions of life sciences, behavioral sciences, chemical sciences, and bioengineering. Provides access to additional relevant web sites and links to other NCBI molecular biology resources. Publishers of journals can submit their citations to NCBI and then provide access to full-text of articles at journal web sites using LinkOut.

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PRISM (tool)

RRID:SCR_005375

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.

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Promega (tool)

RRID:SCR_006724

An Antibody supplier

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Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

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HeLa (tool)

RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

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GST antibody (HRP) (antibody)

RRID:AB_303783

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Anti-β-Actin Antibody (antibody)

RRID:AB_476744

This monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH

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Topoisomerase I antibody [EPR5375] (antibody)

RRID:AB_10861978

This monoclonal targets Topoisomerase I antibody [EPR5375]

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Lamin B1 (D4Q4Z) Rabbit mAb #12586 (antibody)

RRID:AB_2650517

This monoclonal targets Lamin B1

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NOLA1 Antibody (antibody)

RRID:AB_2801566

This polyclonal targets NOLA1 (GAR1)

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BRCA1 Antibody (antibody)

RRID:AB_2228244

This polyclonal targets BRCA1

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DDX42 antibody (antibody)

RRID:AB_2041042

This polyclonal targets Human DDX42

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β-Actin (13E5) Rabbit mAb (antibody)

RRID:AB_2223172

This monoclonal targets beta-Actin

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GAPDH (D16H11) XP Rabbit mAb (antibody)

RRID:AB_10622025

This monoclonal targets GAPDH

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PolySearch (service resource)

RRID:SCR_005291

A web-based tool that supports more than 50 different classes of queries against nearly a dozen different types of text, scientific abstract or bioinformatic databases. The typical query supported by PolySearch is Given X, find all Y''s where X or Y can be diseases, tissues, cell compartments, gene/protein names, SNPs, mutations, drugs and metabolites. PolySearch also exploits a variety of techniques in text mining and information retrieval to identify, highlight and rank informative abstracts, paragraphs or sentences.

View all literature mentions

Cytoscape (software resource)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

View all literature mentions

edgeR (software resource)

RRID:SCR_012802

Bioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.

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Python Programming Language (software resource)

RRID:SCR_008394

Programming language for all operating systems that lets users work more quickly and integrate their systems more effectively. Often compared to Tcl, Perl, Ruby, Scheme or Java. Some of its key distinguishing features include very clear and readable syntax, strong introspection capabilities, intuitive object orientation, natural expression of procedural code, full modularity, exception-based error handling, high level dynamic data types, extensive standard libraries and third party modules for virtually every task, extensions and modules easily written in C, C (or Java for Python, or .NET languages for IronPython), and embeddable within applications as a scripting interface.

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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Bowtie (software resource)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

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ClueGO (software resource)

RRID:SCR_005748

A Cytoscape plug-in that visualizes the non-redundant biological terms for large clusters of genes in a functionally grouped network. It can be used in combination with GOlorize. The identifiers can be uploaded from a text file or interactively from a network of Cytoscape. The type of identifiers supported can be easily extended by the user. ClueGO performs single cluster analysis and comparison of clusters. From the ontology sources used, the terms are selected by different filter criteria. The related terms which share similar associated genes can be combined to reduce redundancy. The ClueGO network is created with kappa statistics and reflects the relationships between the terms based on the similarity of their associated genes. On the network, the node colour can be switched between functional groups and clusters distribution. ClueGO charts are underlying the specificity and the common aspects of the biological role. The significance of the terms and groups is automatically calculated. ClueGO is easy updatable with the newest files from Gene Ontology and KEGG. Platform: Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

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DAVID (software resource)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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FastQC (software resource)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

Plat-A (cell line)

RRID:CVCL_B489

Cell line Plat-A is a Transformed cell line with a species of origin Homo sapiens (Human)

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A-375 (cell line)

RRID:CVCL_0132

Cell line A-375 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HT-1080 (cell line)

RRID:CVCL_0317

Cell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)

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GST antibody (HRP) (antibody)

RRID:AB_303783

This polyclonal targets GST antibody (HRP)

View all literature mentions

GST antibody (HRP) (antibody)

RRID:AB_303783

This polyclonal targets GST antibody (HRP)

View all literature mentions

FastQC (software resource)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

View all literature mentions

DAVID (software resource)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

View all literature mentions

edgeR (software resource)

RRID:SCR_012802

Bioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.

View all literature mentions

ClueGO (software resource)

RRID:SCR_005748

A Cytoscape plug-in that visualizes the non-redundant biological terms for large clusters of genes in a functionally grouped network. It can be used in combination with GOlorize. The identifiers can be uploaded from a text file or interactively from a network of Cytoscape. The type of identifiers supported can be easily extended by the user. ClueGO performs single cluster analysis and comparison of clusters. From the ontology sources used, the terms are selected by different filter criteria. The related terms which share similar associated genes can be combined to reduce redundancy. The ClueGO network is created with kappa statistics and reflects the relationships between the terms based on the similarity of their associated genes. On the network, the node colour can be switched between functional groups and clusters distribution. ClueGO charts are underlying the specificity and the common aspects of the biological role. The significance of the terms and groups is automatically calculated. ClueGO is easy updatable with the newest files from Gene Ontology and KEGG. Platform: Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

View all literature mentions

Bowtie (software resource)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

View all literature mentions

Python Programming Language (software resource)

RRID:SCR_008394

Programming language for all operating systems that lets users work more quickly and integrate their systems more effectively. Often compared to Tcl, Perl, Ruby, Scheme or Java. Some of its key distinguishing features include very clear and readable syntax, strong introspection capabilities, intuitive object orientation, natural expression of procedural code, full modularity, exception-based error handling, high level dynamic data types, extensive standard libraries and third party modules for virtually every task, extensions and modules easily written in C, C (or Java for Python, or .NET languages for IronPython), and embeddable within applications as a scripting interface.

View all literature mentions

Cytoscape (software resource)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

View all literature mentions

PolySearch (service resource)

RRID:SCR_005291

A web-based tool that supports more than 50 different classes of queries against nearly a dozen different types of text, scientific abstract or bioinformatic databases. The typical query supported by PolySearch is Given X, find all Y''s where X or Y can be diseases, tissues, cell compartments, gene/protein names, SNPs, mutations, drugs and metabolites. PolySearch also exploits a variety of techniques in text mining and information retrieval to identify, highlight and rank informative abstracts, paragraphs or sentences.

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

Anti-β-Actin Antibody (antibody)

RRID:AB_476744

This monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH

View all literature mentions