BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors.

Abstract:

:Heterozygous germline mutations in BRCA2 predispose to breast and ovarian cancer. Contrary to non-cancerous cells, where BRCA2 deletion causes cell cycle arrest or cell death, tumors carrying BRCA2 inactivation continue to proliferate. Here we set out to investigate adaptation to loss of BRCA2 focusing on genome-wide transcriptome alterations. Human cells in which BRCA2 expression is inhibited for 4 or 28 days are subjected to RNA-seq analyses revealing a biphasic response to BRCA2 abrogation. The early, acute response consists of downregulation of genes involved in cell cycle progression, DNA replication and repair and is associated with cell cycle arrest in G1. Surprisingly, the late, chronic response consists predominantly of upregulation of interferon-stimulated genes (ISGs). Activation of the cGAS-STING-STAT pathway detected in these cells further substantiates the concept that BRCA2 abrogation triggers cell-intrinsic immune signaling. Importantly, we find that treatment with PARP inhibitors stimulates the interferon response in cells and tumors lacking BRCA2.

journal_name

Nat Commun

journal_title

Nature communications

authors

Reisländer T,Lombardi EP,Groelly FJ,Miar A,Porru M,Di Vito S,Wright B,Lockstone H,Biroccio A,Harris A,Londoño-Vallejo A,Tarsounas M

doi

10.1038/s41467-019-11048-5

subject

Has Abstract

pub_date

2019-07-17 00:00:00

pages

3143

issue

1

issn

2041-1723

pii

10.1038/s41467-019-11048-5

journal_volume

10

pub_type

杂志文章
  • Three-dimensional structural dynamics of DNA origami Bennett linkages using individual-particle electron tomography.

    abstract::Scaffolded DNA origami has proven to be a powerful and efficient technique to fabricate functional nanomachines by programming the folding of a single-stranded DNA template strand into three-dimensional (3D) nanostructures, designed to be precisely motion-controlled. Although two-dimensional (2D) imaging of DNA nanoma...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-03018-0

    authors: Lei D,Marras AE,Liu J,Huang CM,Zhou L,Castro CE,Su HJ,Ren G

    更新日期:2018-02-09 00:00:00

  • Allele-aware chromosome-level genome assembly and efficient transgene-free genome editing for the autotetraploid cultivated alfalfa.

    abstract::Artificially improving traits of cultivated alfalfa (Medicago sativa L.), one of the most important forage crops, is challenging due to the lack of a reference genome and an efficient genome editing protocol, which mainly result from its autotetraploidy and self-incompatibility. Here, we generate an allele-aware chrom...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-16338-x

    authors: Chen H,Zeng Y,Yang Y,Huang L,Tang B,Zhang H,Hao F,Liu W,Li Y,Liu Y,Zhang X,Zhang R,Zhang Y,Li Y,Wang K,He H,Wang Z,Fan G,Yang H,Bao A,Shang Z,Chen J,Wang W,Qiu Q

    更新日期:2020-05-19 00:00:00

  • Differential contribution of transcriptomic regulatory layers in the definition of neuronal identity.

    abstract::Previous transcriptomic profiling studies have typically focused on separately analyzing mRNA expression, alternative splicing and alternative polyadenylation differences between cell and tissue types. However, the relative contribution of these three transcriptomic regulatory layers to cell type specification is poor...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-20483-8

    authors: Ha KCH,Sterne-Weiler T,Morris Q,Weatheritt RJ,Blencowe BJ

    更新日期:2021-01-12 00:00:00

  • APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma.

    abstract::We have sequenced 463 presenting cases of myeloma entered into the UK Myeloma XI study using whole exome sequencing. Here we identify mutations induced as a consequence of misdirected AID in the partner oncogenes of IGH translocations, which are activating and associated with impaired clinical outcome. An APOBEC mutat...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7997

    authors: Walker BA,Wardell CP,Murison A,Boyle EM,Begum DB,Dahir NM,Proszek PZ,Melchor L,Pawlyn C,Kaiser MF,Johnson DC,Qiang YW,Jones JR,Cairns DA,Gregory WM,Owen RG,Cook G,Drayson MT,Jackson GH,Davies FE,Morgan GJ

    更新日期:2015-04-23 00:00:00

  • Author Correction: Molecular vibrations reduce the maximum achievable photovoltage in organic solar cells.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature communications

    pub_type: 已发布勘误

    doi:10.1038/s41467-020-15790-z

    authors: Panhans M,Hutsch S,Benduhn J,Schellhammer KS,Nikolis VC,Vangerven T,Vandewal K,Ortmann F

    更新日期:2020-04-22 00:00:00

  • Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma.

    abstract::Aortic dissection and intramural haematoma comprise an aortopathy involving separation of the aortic wall. Underlying mechanisms of the condition remain unclear. Here we show that granulocyte macrophage colony-stimulating factor (GM-CSF) is a triggering molecule for this condition. Transcription factor Krüppel-like fa...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7994

    authors: Son BK,Sawaki D,Tomida S,Fujita D,Aizawa K,Aoki H,Akishita M,Manabe I,Komuro I,Friedman SL,Nagai R,Suzuki T

    更新日期:2015-04-29 00:00:00

  • Polarization curling and flux closures in multiferroic tunnel junctions.

    abstract::Formation of domain walls in ferroelectrics is not energetically favourable in low-dimensional systems. Instead, vortex-type structures are formed that are driven by depolarization fields occurring in such systems. Consequently, polarization vortices have only been experimentally found in systems in which these fields...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13484

    authors: Peters JJP,Apachitei G,Beanland R,Alexe M,Sanchez AM

    更新日期:2016-11-16 00:00:00

  • Confinement-deconfinement transition due to spontaneous symmetry breaking in quantum Hall bilayers.

    abstract::Band-inverted electron-hole bilayers support quantum spin Hall insulator and exciton condensate phases. Interest in quantum spin Hall effect in these systems has recently put them in the spotlight. We investigate such a bilayer in an external magnetic field. We show that the interlayer correlations lead to formation o...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10462

    authors: Pikulin DI,Silvestrov PG,Hyart T

    更新日期:2016-01-25 00:00:00

  • Understanding the role of phase in chemical bond breaking with coincidence angular streaking.

    abstract::Electron motion in chemical bonds occurs on an attosecond timescale. This ultrafast motion can be driven by strong laser fields. Ultrashort asymmetric laser pulses are known to direct electrons to a certain direction. But do symmetric laser pulses destroy symmetry in breaking chemical bonds? Here we answer this questi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3177

    authors: Wu J,Magrakvelidze M,Schmidt LP,Kunitski M,Pfeifer T,Schöffler M,Pitzer M,Richter M,Voss S,Sann H,Kim H,Lower J,Jahnke T,Czasch A,Thumm U,Dörner R

    更新日期:2013-01-01 00:00:00

  • Size-dependent diffusion controls natural aging in aluminium alloys.

    abstract::A key question in materials science is how fast properties evolve, which relates to the kinetics of phase transformations. In metals, kinetics is primarily connected to diffusion, which for substitutional elements is enabled via mobile atomic-lattice vacancies. In fact, non-equilibrium vacancies are often required for...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-12762-w

    authors: Dumitraschkewitz P,Uggowitzer PJ,Gerstl SSA,Löffler JF,Pogatscher S

    更新日期:2019-10-18 00:00:00

  • Environment-responsive nanophores for therapy and treatment monitoring via molecular MRI quenching.

    abstract::The effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we demonstrate that clinically approved iron oxide nanoparticles (Ferumoxytol) can be utilized to carry one or multiple drugs. These so called 'nanophores' retain their cargo within their po...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4384

    authors: Kaittanis C,Shaffer TM,Ogirala A,Santra S,Perez JM,Chiosis G,Li Y,Josephson L,Grimm J

    更新日期:2014-03-04 00:00:00

  • Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice.

    abstract::VRC01-class broadly neutralizing HIV-1 antibodies protect animals from experimental infection and could contribute to an effective vaccine response. Their predicted germline forms (gl) bind Env inefficiently, which may explain why they are not elicited by HIV-1 Env-immunization. Here we show that an optimized Env immu...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10618

    authors: McGuire AT,Gray MD,Dosenovic P,Gitlin AD,Freund NT,Petersen J,Correnti C,Johnsen W,Kegel R,Stuart AB,Glenn J,Seaman MS,Schief WR,Strong RK,Nussenzweig MC,Stamatatos L

    更新日期:2016-02-24 00:00:00

  • Hydrogen spillover through Matryoshka-type (ZIFs@)n-1ZIFs nanocubes.

    abstract::Hydrogen spillover phenomenon is well-documented in hydrogenation catalysis but still highly disputed in hydrogen storage. Until now, the existence of hydrogen spillover through metal-organic frameworks (MOFs) remains a topic of ongoing debate and how far the split hydrogen atoms diffuse in such materials is unknown. ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-06269-z

    authors: Zhan G,Zeng HC

    更新日期:2018-09-17 00:00:00

  • Photosynthesis-dependent H2O2 transfer from chloroplasts to nuclei provides a high-light signalling mechanism.

    abstract::Chloroplasts communicate information by signalling to nuclei during acclimation to fluctuating light. Several potential operating signals originating from chloroplasts have been proposed, but none have been shown to move to nuclei to modulate gene expression. One proposed signal is hydrogen peroxide (H2O2) produced by...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00074-w

    authors: Exposito-Rodriguez M,Laissue PP,Yvon-Durocher G,Smirnoff N,Mullineaux PM

    更新日期:2017-06-29 00:00:00

  • Maturation of the HIV-1 core by a non-diffusional phase transition.

    abstract::The formation of the HIV-1 core is the final step in the viral maturation pathway, resulting in the formation of infectious virus. Most current models for HIV-1 core formation suggest that, upon proteolytic cleavage from the immature Gag, capsid (CA) dissociates into the viral interior before reforming into the core. ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6854

    authors: Frank GA,Narayan K,Bess JW Jr,Del Prete GQ,Wu X,Moran A,Hartnell LM,Earl LA,Lifson JD,Subramaniam S

    更新日期:2015-01-08 00:00:00

  • Olfactory specificity regulates lipid metabolism through neuroendocrine signaling in Caenorhabditis elegans.

    abstract::Olfactory and metabolic dysfunctions are intertwined phenomena associated with obesity and neurodegenerative diseases; yet how mechanistically olfaction regulates metabolic homeostasis remains unclear. Specificity of olfactory perception integrates diverse environmental odors and olfactory neurons expressing different...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15296-8

    authors: Mutlu AS,Gao SM,Zhang H,Wang MC

    更新日期:2020-03-19 00:00:00

  • Shape-memory effects in molecular crystals.

    abstract::Molecular crystals can be bent elastically by expansion or plastically by delamination into slabs that glide along slip planes. Here we report that upon bending, terephthalic acid crystals can undergo a mechanically induced phase transition without delamination and their overall crystal integrity is retained. Such pla...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-11612-z

    authors: Ahmed E,Karothu DP,Warren M,Naumov P

    更新日期:2019-08-19 00:00:00

  • The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development.

    abstract::Streptomycetes are notable for their complex life cycle and production of most clinically important antibiotics. A key factor that controls entry into development and the onset of antibiotic production is the 68-residue protein, BldC. BldC is a putative DNA-binding protein related to MerR regulators, but lacks coiled-...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-03576-3

    authors: Schumacher MA,den Hengst CD,Bush MJ,Le TBK,Tran NT,Chandra G,Zeng W,Travis B,Brennan RG,Buttner MJ

    更新日期:2018-03-19 00:00:00

  • Alkaline earth metal vanadates as sodium-ion battery anodes.

    abstract::The abundance of sodium resources indicates the potential of sodium-ion batteries as emerging energy storage devices. However, the practical application of sodium-ion batteries is hindered by the limited electrochemical performance of electrode materials, especially at the anode side. Here, we identify alkaline earth ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00211-5

    authors: Xu X,Niu C,Duan M,Wang X,Huang L,Wang J,Pu L,Ren W,Shi C,Meng J,Song B,Mai L

    更新日期:2017-09-06 00:00:00

  • Gingival solitary chemosensory cells are immune sentinels for periodontitis.

    abstract::Solitary chemosensory cells (SCCs) are epithelial sentinels that utilize bitter Tas2r receptors and coupled taste transduction elements to detect pathogenic bacterial metabolites, triggering host defenses to control the infection. Here we report that SCCs are present in mouse gingival junctional epithelium, where they...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-12505-x

    authors: Zheng X,Tizzano M,Redding K,He J,Peng X,Jiang P,Xu X,Zhou X,Margolskee RF

    更新日期:2019-10-03 00:00:00

  • An activity-dependent proximity ligation platform for spatially resolved quantification of active enzymes in single cells.

    abstract::Integration of chemical probes into proteomic workflows enables the interrogation of protein activity, rather than abundance. Current methods limit the biological contexts that can be addressed due to sample homogenization, signal-averaging, and bias toward abundant proteins. Here we report a platform that integrates ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01854-0

    authors: Li G,Montgomery JE,Eckert MA,Chang JW,Tienda SM,Lengyel E,Moellering RE

    更新日期:2017-11-24 00:00:00

  • Ligands with 1,10-phenanthroline scaffold for highly regioselective iron-catalyzed alkene hydrosilylation.

    abstract::Transition-metal-catalyzed alkene hydrosilylation is one of the most important homogeneous catalytic reactions, and the development of methods that use base metals, especially iron, as catalysts for this transformation is a growing area of research. However, the limited number of ligand scaffolds applicable for base-m...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-02472-6

    authors: Hu MY,He Q,Fan SJ,Wang ZC,Liu LY,Mu YJ,Peng Q,Zhu SF

    更新日期:2018-01-15 00:00:00

  • Bulk tissue cell type deconvolution with multi-subject single-cell expression reference.

    abstract::Knowledge of cell type composition in disease relevant tissues is an important step towards the identification of cellular targets of disease. We present MuSiC, a method that utilizes cell-type specific gene expression from single-cell RNA sequencing (RNA-seq) data to characterize cell type compositions from bulk RNA-...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-08023-x

    authors: Wang X,Park J,Susztak K,Zhang NR,Li M

    更新日期:2019-01-22 00:00:00

  • Opposing effects of target overexpression reveal drug mechanisms.

    abstract::Overexpression of a drug's molecular target often increases drug resistance, offering a pathway for adaptive evolution and a tool for target identification. It is unclear though why this phenomenon applies to some drugs but not others. Here we gradually overexpressed antibiotic targets in Escherichia coli and found th...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5296

    authors: Palmer AC,Kishony R

    更新日期:2014-07-01 00:00:00

  • Structural basis of IL-23 antagonism by an Alphabody protein scaffold.

    abstract::Protein scaffolds can provide a promising alternative to antibodies for various biomedical and biotechnological applications, including therapeutics. Here we describe the design and development of the Alphabody, a protein scaffold featuring a single-chain antiparallel triple-helix coiled-coil fold. We report affinity-...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6237

    authors: Desmet J,Verstraete K,Bloch Y,Lorent E,Wen Y,Devreese B,Vandenbroucke K,Loverix S,Hettmann T,Deroo S,Somers K,Henderikx P,Lasters I,Savvides SN

    更新日期:2014-10-30 00:00:00

  • Two-dimensional molecular brush-functionalized porous bilayer composite separators toward ultrastable high-current density lithium metal anodes.

    abstract::Lithium metal batteries have been considerably limited by the problems of uncontrolled dendritic lithium formation and the highly reactive nature of lithium with electrolytes. Herein, we have developed functional porous bilayer composite separators by simply blade-coating polyacrylamide-grafted graphene oxide molecula...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09211-z

    authors: Li C,Liu S,Shi C,Liang G,Lu Z,Fu R,Wu D

    更新日期:2019-03-25 00:00:00

  • Vascular channels formed by subpopulations of PECAM1+ melanoma cells.

    abstract::Targeting the vasculature remains a promising approach for treating solid tumours; however, the mechanisms of tumour neovascularization are diverse and complex. Here we uncover a new subpopulation of melanoma cells that express the vascular cell adhesion molecule PECAM1, but not VEGFR-2, and participate in a PECAM1-de...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6200

    authors: Dunleavey JM,Xiao L,Thompson J,Kim MM,Shields JM,Shelton SE,Irvin DM,Brings VE,Ollila DW,Brekken RA,Dayton PA,Melero-Martin JM,Dudley AC

    更新日期:2014-10-22 00:00:00

  • Atypical chemoreceptor arrays accommodate high membrane curvature.

    abstract::The prokaryotic chemotaxis system is arguably the best-understood signaling pathway in biology. In all previously described species, chemoreceptors organize into a hexagonal (P6 symmetry) extended array. Here, we report an alternative symmetry (P2) of the chemotaxis apparatus that emerges from a strict linear organiza...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-19628-6

    authors: Muok AR,Ortega DR,Kurniyati K,Yang W,Maschmann ZA,Sidi Mabrouk A,Li C,Crane BR,Briegel A

    更新日期:2020-11-13 00:00:00

  • Fast growth of large-grain and continuous MoS2 films through a self-capping vapor-liquid-solid method.

    abstract::Most chemical vapor deposition methods for transition metal dichalcogenides use an extremely small amount of precursor to render large single-crystal flakes, which usually causes low coverage of the materials on the substrate. In this study, a self-capping vapor-liquid-solid reaction is proposed to fabricate large-gra...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-17517-6

    authors: Chang MC,Ho PH,Tseng MF,Lin FY,Hou CH,Lin IK,Wang H,Huang PP,Chiang CH,Yang YC,Wang IT,Du HY,Wen CY,Shyue JJ,Chen CW,Chen KH,Chiu PW,Chen LC

    更新日期:2020-07-23 00:00:00

  • A metal-free electrocatalyst for carbon dioxide reduction to multi-carbon hydrocarbons and oxygenates.

    abstract::Electroreduction of carbon dioxide into higher-energy liquid fuels and chemicals is a promising but challenging renewable energy conversion technology. Among the electrocatalysts screened so far for carbon dioxide reduction, which includes metals, alloys, organometallics, layered materials and carbon nanostructures, o...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13869

    authors: Wu J,Ma S,Sun J,Gold JI,Tiwary C,Kim B,Zhu L,Chopra N,Odeh IN,Vajtai R,Yu AZ,Luo R,Lou J,Ding G,Kenis PJ,Ajayan PM

    更新日期:2016-12-13 00:00:00