当前位置： SCI文献检索 > NATURE期刊下所有文献 > Replication fork stability confers chemoresistance in BRCA-deficient cells.

Replication fork stability confers chemoresistance in BRCA-deficient cells.

Abstract：

:Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of replication fork protection, highlighting the complexities by which tumour cells evade chemotherapeutic interventions and acquire drug resistance.

journal_name

Nature

journal_title

Nature

authors

Ray Chaudhuri A,Callen E,Ding X,Gogola E,Duarte AA,Lee JE,Wong N,Lafarga V,Calvo JA,Panzarino NJ,John S,Day A,Crespo AV,Shen B,Starnes LM,de Ruiter JR,Daniel JA,Konstantinopoulos PA,Cortez D,Cantor SB,Fernandez-Ca

doi

10.1038/nature18325

subject

Has Abstract

pub_date

2016-07-21 00:00:00

pages

382-7

issue

7612

eissn

0028-0836

issn

1476-4687

pii

nature18325

journal_volume

535

pub_type

杂志文章

相关文献

NATURE文献大全
  • Mouse genomic variation and its effect on phenotypes and gene regulation.

    abstract：:We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known. We use these genomes to explore the phylogenetic history of the laboratory mouse and to examine the functional consequences of allele-specific variation on transcript abundance, reveali...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature10413

    authors： Keane TM,Goodstadt L,Danecek P,White MA,Wong K,Yalcin B,Heger A,Agam A,Slater G,Goodson M,Furlotte NA,Eskin E,Nellåker C,Whitley H,Cleak J,Janowitz D,Hernandez-Pliego P,Edwards A,Belgard TG,Oliver PL,McIntyre RE,

    更新日期：2011-09-14 00:00:00

  • California's methane super-emitters.

    abstract：:Methane is a powerful greenhouse gas and is targeted for emissions mitigation by the US state of California and other jurisdictions worldwide1,2. Unique opportunities for mitigation are presented by point-source emitters-surface features or infrastructure components that are typically less than 10 metres in diameter a...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/s41586-019-1720-3

    authors： Duren RM,Thorpe AK,Foster KT,Rafiq T,Hopkins FM,Yadav V,Bue BD,Thompson DR,Conley S,Colombi NK,Frankenberg C,McCubbin IB,Eastwood ML,Falk M,Herner JD,Croes BE,Green RO,Miller CE

    更新日期：2019-11-01 00:00:00

  • Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.

    abstract：:Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-sel...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature11375

    authors： Baconguis I,Gouaux E

    更新日期：2012-09-20 00:00:00

  • Origin of luteinizing hormone-releasing hormone neurons.

    abstract：:Neurons expressing luteinizing hormone-releasing hormone (LHRH), found in the septal-preoptic nuclei and hypothalamus, control the release of gonadotropic hormones from the anterior pituitary gland and facilitate reproductive behaviour. LHRH-expressing neurons are also found in the nervus terminalis, a cranial nerve t...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/338161a0

    authors： Schwanzel-Fukuda M,Pfaff DW

    更新日期：1989-03-09 00:00:00

  • Genetic hypertension in rats is accompanied by a defect in renal prostaglandin catabolism.

    abstract：:Noradrenaline releases prostaglandins in the kidney, and in rats these augment rather than reduce vasoconstriction produced by the amine. Homogenates of kidneys of New Zealand rats inbred for hypertension exhibit lower prostaglandin inactivation by 15-hydroxydehydrogenase than controls. At the same time, augmentation ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/260582a0

    authors： Armstrong JM,Blackwell GJ,Flower RJ,McGiff JC,Mullane KM,Vane JR

    更新日期：1976-04-15 00:00:00

  • Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus.

    abstract：:Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown. Genetic linkage has been investigated in multigeneration families to localize, and ultimately identify,...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/356162a0

    authors： Froguel P,Vaxillaire M,Sun F,Velho G,Zouali H,Butel MO,Lesage S,Vionnet N,Clément K,Fougerousse F

    更新日期：1992-03-12 00:00:00

  • Vector-based navigation using grid-like representations in artificial agents.

    abstract：:Deep neural networks have achieved impressive successes in fields ranging from object recognition to complex games such as Go1,2. Navigation, however, remains a substantial challenge for artificial agents, with deep neural networks trained by reinforcement learning3-5 failing to rival the proficiency of mammalian spat...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/s41586-018-0102-6

    authors： Banino A,Barry C,Uria B,Blundell C,Lillicrap T,Mirowski P,Pritzel A,Chadwick MJ,Degris T,Modayil J,Wayne G,Soyer H,Viola F,Zhang B,Goroshin R,Rabinowitz N,Pascanu R,Beattie C,Petersen S,Sadik A,Gaffney S,King H

    更新日期：2018-05-01 00:00:00

  • Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere.

    abstract：:Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei. Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes. At...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature12663

    authors： Almeida J,Schobesberger S,Kürten A,Ortega IK,Kupiainen-Määttä O,Praplan AP,Adamov A,Amorim A,Bianchi F,Breitenlechner M,David A,Dommen J,Donahue NM,Downard A,Dunne E,Duplissy J,Ehrhart S,Flagan RC,Franchin A,Guida R

    更新日期：2013-10-17 00:00:00

  • Biodiversity conservation: effects of changes in climate and land use.

    abstract：:Thomas et al. argue, contrary to Sala et al. that climate change poses an equal or greater threat to global biodiversity than land-use change. We contest this claim, however, on the grounds that Thomas et al. incorrectly apply species-area relationships. ...

    journal_title：Nature

    pub_type： 评论,杂志文章

    doi：10.1038/nature02717

    authors： Buckley LB,Roughgarden J

    更新日期：2004-07-01 00:00:00

  • Alcohol-derived DNA crosslinks are repaired by two distinct mechanisms.

    abstract：:Acetaldehyde is a highly reactive, DNA-damaging metabolite that is produced upon alcohol consumption1. Impaired detoxification of acetaldehyde is common in the Asian population, and is associated with alcohol-related cancers1,2. Cells are protected against acetaldehyde-induced damage by DNA crosslink repair, which whe...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/s41586-020-2059-5

    authors： Hodskinson MR,Bolner A,Sato K,Kamimae-Lanning AN,Rooijers K,Witte M,Mahesh M,Silhan J,Petek M,Williams DM,Kind J,Chin JW,Patel KJ,Knipscheer P

    更新日期：2020-03-01 00:00:00

  • Morphology and intracortical projections of functionally characterised neurones in the cat visual cortex.

    abstract：:The neuronal structure and connectivity underlying receptive field organisation of cells in the cat visual cortex have been investigated. Intracellular recordings were made using a micropipette filled with a histochemical marker, which was injected into the cells after their receptive fields had been characterised. Th...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/280120a0

    authors： Gilbert CD,Wiesel TN

    更新日期：1979-07-12 00:00:00

  • Articulated Palaeozoic fossil with 17 plates greatly expands disparity of early chitons.

    abstract：:Modern chitons (Mollusca: Polyplacophora) possess a highly conserved skeleton of eight shell plates (valves) surrounded by spicules or scales, and fossil evidence suggests that the chiton skeleton has changed little since the first appearance of the class in the Late Cambrian period (about 500 million years before pre...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature02548

    authors： Vendrasco MJ,Wood TE,Runnegar BN

    更新日期：2004-05-20 00:00:00

  • A crystallizing dense magma ocean at the base of the Earth's mantle.

    abstract：:The distribution of geochemical species in the Earth's interior is largely controlled by fractional melting and crystallization processes that are intimately linked to the thermal state and evolution of the mantle. The existence of patches of dense partial melt at the base of the Earth's mantle, together with estimate...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature06355

    authors： Labrosse S,Hernlund JW,Coltice N

    更新日期：2007-12-06 00:00:00

  • Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer.

    abstract：:Brain metastasis represents a substantial source of morbidity and mortality in various cancers, and is characterized by high resistance to chemotherapy. Here we define the role of the most abundant cell type in the brain, the astrocyte, in promoting brain metastasis. We show that human and mouse breast and lung cancer...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature18268

    authors： Chen Q,Boire A,Jin X,Valiente M,Er EE,Lopez-Soto A,Jacob L,Patwa R,Shah H,Xu K,Cross JR,Massagué J

    更新日期：2016-05-26 00:00:00

  • Gene expression variability across cells and species shapes innate immunity.

    abstract：:As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/s41586-018-0657-2

    authors： Hagai T,Chen X,Miragaia RJ,Rostom R,Gomes T,Kunowska N,Henriksson J,Park JE,Proserpio V,Donati G,Bossini-Castillo L,Vieira Braga FA,Naamati G,Fletcher J,Stephenson E,Vegh P,Trynka G,Kondova I,Dennis M,Haniffa M,No

    更新日期：2018-11-01 00:00:00

  • Patterns of colonization in a metapopulation of grey seals.

    abstract：:The colonization of a new habitat is a fundamental process in metapopulation biology, but it is difficult to study. The emigration of colonists from established populations might be induced by resource competition owing to high local population density. Migration distances are also important because they determine the...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/416424a

    authors： Gaggiotti OE,Jones F,Lee WM,Amos W,Harwood J,Nichols RA

    更新日期：2002-03-28 00:00:00

  • Association between GTPase activators for Rho and Ras families.

    abstract：:The ras-related low-molecular-mass GTPases participate in signal transduction involving a variety of cellular functions, including cell-cycle progression, cellular differentiation, cytoskeletal organization, protein transport and secretion. The cycling of these proteins between GTP-bound and GDP-bound states is partia...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/359153a0

    authors： Settleman J,Albright CF,Foster LC,Weinberg RA

    更新日期：1992-09-10 00:00:00

  • Aged murine killer T-cell clones acquire specific cytotoxicity for P815 mastocytoma cells.

    abstract：:T-cell clones that grow continuously in tissue culture have become a major tool for studying the properties of T lymphocytes. It is therefore important to know to what extent such clones resemble their normal counterparts. Several reports have appeared recently which demonstrate that long-term T-cell lines may lose th...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/308367a0

    authors： Simon MM,Weltzien HU,Bühring HJ,Eichmann K

    更新日期：1984-03-22 00:00:00

  • 'Mining' Bitcoin takes more energy than mining gold.

    abstract：: ...

    journal_title：Nature

    pub_type： 新闻

    doi：10.1038/d41586-018-07283-3

    authors：

    更新日期：2018-11-01 00:00:00

  • Cryptochrome mediates light-dependent magnetosensitivity in Drosophila.

    abstract：:Although many animals use the Earth's magnetic field for orientation and navigation, the precise biophysical mechanisms underlying magnetic sensing have been elusive. One theoretical model proposes that geomagnetic fields are perceived by chemical reactions involving specialized photoreceptors. However, the specific p...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature07183

    authors： Gegear RJ,Casselman A,Waddell S,Reppert SM

    更新日期：2008-08-21 00:00:00

  • Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells.

    abstract：:Stable maintenance of gene regulatory programs is essential for normal function in multicellular organisms. Epigenetic mechanisms, and DNA methylation in particular, are hypothesized to facilitate such maintenance by creating cellular memory that can be written during embryonic development and then guide cell-type-spe...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature13458

    authors： Shipony Z,Mukamel Z,Cohen NM,Landan G,Chomsky E,Zeliger SR,Fried YC,Ainbinder E,Friedman N,Tanay A

    更新日期：2014-09-04 00:00:00

  • Control of X chromosome transcription by the maleless gene in Drosophila.

    abstract：:In Drosophila, a large group of structural genes exhibit coordinate regulation, not because they function in a common developmental pathway but because they happen to reside on the X chromosome. These genes are subjected to the regulatory mechanism of dosage compensation which insures that their phenotypic products ar...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/285573a0

    authors： Belote JM,Lucchesi JC

    更新日期：1980-06-19 00:00:00

  • Homology of Ti alpha-subunit of a T-cell antigen-MHC receptor with immunoglobulin.

    abstract：:Human T-cell receptors for antigen and major histocompatibility complex (MHC) determinants have now been defined on inducer, suppressor, and class 1 and class 2 MHC-specific cytotoxic T lymphocytes as T3-associated clonotypic molecules (Ti) of relative molecular mass 90,000 (90K) composed of one 49-54K alpha- and one ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/312269a0

    authors： Fabbi M,Acuto O,Smart JE,Reinherz EL

    更新日期：1984-11-15 00:00:00

  • Evidence for a viral superantigen in humans.

    abstract：:Superantigens bind class II major histocompatibility proteins and stimulate powerful proliferative responses of T lymphocytes bearing particular V beta sequences as part of their alpha beta antigen receptor. Exogenous bacterial superantigens are responsible for food poisoning and toxic shock syndrome. Murine virus-enc...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/358507a0

    authors： Lafon M,Lafage M,Martinez-Arends A,Ramirez R,Vuillier F,Charron D,Lotteau V,Scott-Algara D

    更新日期：1992-08-06 00:00:00

  • A framework for human microbiome research.

    abstract：:A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resu...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature11209

    authors： Human Microbiome Project Consortium.

    更新日期：2012-06-13 00:00:00

  • Magnetite defines a vertebrate magnetoreceptor.

    abstract：:The key behavioural, physiological and anatomical components of a magnetite-based magnetic sense have been demonstrated in rainbow trout (Oncorhynchus mykiss). Candidate receptor cells located within a discrete sub-layer of the olfactory lamellae contained iron-rich crystals that were similar in size and shape to magn...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/35018561

    authors： Diebel CE,Proksch R,Green CR,Neilson P,Walker MM

    更新日期：2000-07-20 00:00:00

  • Author Correction: Autophagy maintains tumour growth through circulating arginine.

    abstract：:In this Letter, 'released' should have been 'regulated' in the sentence starting: 'Deletion of Atg5 in the host similarly regulated circulating arginine and suppressed tumorigenesis...' This has been corrected online. ...

    journal_title：Nature

    pub_type： 杂志文章,已发布勘误

    doi：10.1038/s41586-018-0815-6

    authors： Poillet-Perez L,Xie X,Zhan L,Yang Y,Sharp DW,Hu ZS,Su X,Maganti A,Jiang C,Lu W,Zheng H,Bosenberg MW,Mehnert JM,Guo JY,Lattime E,Rabinowitz JD,White E

    更新日期：2019-01-01 00:00:00

  • Ben Barres: neuroscience pioneer, gender champion.

    abstract：: ...

    journal_title：Nature

    pub_type： 新闻

    doi：10.1038/d41586-018-07109-2

    authors： Freeman M

    更新日期：2018-10-01 00:00:00

  • Microtubule-motor activity of a yeast centromere-binding protein complex.

    abstract：:During cell division, sister chromosomes segregate from each other on a microtubule-based structure called the mitotic spindle. Proteins bind to the centromere, a region of chromosomal DNA, to form the kinetochore, which mediates chromosome attachment to the mitotic spindle microtubules. In the budding yeast Saccharom...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/359533a0

    authors： Hyman AA,Middleton K,Centola M,Mitchison TJ,Carbon J

    更新日期：1992-10-08 00:00:00

  • Effect of cell history on response to helix-loop-helix family of myogenic regulators.

    abstract：:In multinucleated heterokaryons formed from the fusion of differentiated muscle cells to either hepatocytes or fibroblasts, muscle-specific gene expression is activated, liver-specific gene expression is repressed, and there are changes in the location of the Golgi apparatus. An understanding of the regulatory mechani...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/344454a0

    authors： Schäfer BW,Blakely BT,Darlington GJ,Blau HM

    更新日期：1990-03-29 00:00:00