Abstract：
:Genome instability is central to ageing, cancer and other diseases. It is not only proteins involved in DNA replication or the DNA damage response (DDR) that are important for maintaining genome integrity: from yeast to higher eukaryotes, mutations in genes involved in pre-mRNA splicing and in the biogenesis and export of messenger ribonucleoprotein (mRNP) also induce DNA damage and genome instability. This instability is frequently mediated by R-loops formed by DNA-RNA hybrids and a displaced single-stranded DNA. Here we show that the human TREX-2 complex, which is involved in mRNP biogenesis and export, prevents genome instability as determined by the accumulation of γ-H2AX (Ser-139 phosphorylated histone H2AX) and 53BP1 foci and single-cell electrophoresis in cells depleted of the TREX-2 subunits PCID2, GANP and DSS1. We show that the BRCA2 repair factor, which binds to DSS1, also associates with PCID2 in the cell. The use of an enhanced green fluorescent protein-tagged hybrid-binding domain of RNase H1 and the S9.6 antibody did not detect R-loops in TREX-2-depleted cells, but did detect the accumulation of R-loops in BRCA2-depleted cells. The results indicate that R-loops are frequently formed in cells and that BRCA2 is required for their processing. This link between BRCA2 and RNA-mediated genome instability indicates that R-loops may be a chief source of replication stress and cancer-associated instability.
journal_name
Naturejournal_title
Natureauthors
Bhatia V,Barroso SI,García-Rubio ML,Tumini E,Herrera-Moyano E,Aguilera Adoi
10.1038/nature13374subject
Has Abstractpub_date
2014-07-17 00:00:00pages
362-5issue
7509eissn
0028-0836issn
1476-4687pii
nature13374journal_volume
511pub_type
杂志文章相关文献
NATURE文献大全abstract：:Plant respiration results in an annual flux of carbon dioxide (CO2) to the atmosphere that is six times as large as that due to the emissions from fossil fuel burning, so changes in either will impact future climate. As plant respiration responds positively to temperature, a warming world may result in additional resp...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature17142
更新日期：2016-03-31 00:00:00
abstract：:Two principals in the once-raging debate over forensic DNA typing conclude that the scientific issues have all been resolved. ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/371735a0
更新日期：1994-10-27 00:00:00
abstract：:Relapsed acute lymphoblastic leukaemia (ALL) is a leading cause of death due to disease in young people, but the biological determinants of treatment failure remain poorly understood. Recent genome-wide profiling of structural DNA alterations in ALL have identified multiple submicroscopic somatic mutations targeting k...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09727
更新日期：2011-03-10 00:00:00
abstract：:Long-term potentiation (LTP) in the hippocampus is widely studied as the mechanisms involved in its induction and maintenance are believed to underlie fundamental properties of learning and memory in vertebrates. Most synapses that exhibit LTP use an excitatory amino-acid neurotransmitter that acts on two types of rec...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/338500a0
更新日期：1989-04-06 00:00:00
abstract：:Diseases of the vascular system result from a complex mixture of genetic and environmental factors. Data sets, technologies and strategies emanating from the human genome programme have been applied to the analysis of both rare single-gene and common multigenic vascular disorders. Genomic approaches including inter- a...
journal_title：Nature
pub_type： 杂志文章,评审
doi：10.1038/35025236
更新日期：2000-09-14 00:00:00
abstract：:Leukaemia inhibitory factor (LIF) has a variety of effects on different cell types in vitro, inhibiting the differentiation of embryonic stem cells and promoting the survival and/or proliferation of primitive haematopoietic precursors and primordial germ cells. Here we show that LIF-deficient mice derived by gene targ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/363361a0
更新日期：1993-05-27 00:00:00
abstract：:The recent decades-long decline in East African rainfall suggests that multidecadal variability is an important component of the climate of this vulnerable region. Prior work based on analysing the instrumental record implicates both Indian and Pacific ocean sea surface temperatures (SSTs) as possible drivers of East ...
journal_title：Nature
pub_type： 历史文章,杂志文章
doi：10.1038/nature11785
更新日期：2013-01-17 00:00:00
abstract：:The unusual helium-rich (type Ib) supernova SN 2005E is distinguished from all supernovae hitherto observed by its faint and rapidly fading light curve, prominent calcium lines in late-phase spectra and lack of any mark of recent star formation near the supernova location. These properties are claimed to be explained ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09055
更新日期：2010-05-20 00:00:00
abstract：: ...
journal_title：Nature
pub_type： 新闻
doi：10.1038/d41586-018-06989-8
更新日期：2018-10-01 00:00:00
abstract：:The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with more than 780,000 deaths worldwide (as of 20 August 2020). To develop antiviral interventions quickly, drugs used for the treatment of unrelated diseases are curre...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-2575-3
更新日期：2020-09-01 00:00:00
abstract：:The accumulation of somatic DNA damage has been implicated as a cause of ageing in metazoa. One possible mechanism by which increased DNA damage could lead to cellular degeneration and death is by stochastic deregulation of gene expression. Here we directly test for increased transcriptional noise in aged tissue by di...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature04844
更新日期：2006-06-22 00:00:00
abstract：:Nuclear magic numbers correspond to fully occupied energy shells of protons or neutrons inside atomic nuclei. Doubly magic nuclei, with magic numbers for both protons and neutrons, are spherical and extremely rare across the nuclear landscape. Although the sequence of magic numbers is well established for stable nucle...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-019-1155-x
更新日期：2019-05-01 00:00:00
abstract：:Human-mediated translocation of species to areas beyond their natural distribution (which results in 'alien' populations1) is a key signature of the Anthropocene2, and is a primary global driver of biodiversity loss and environmental change3. Stemming the tide of invasions requires understanding why some species fail ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-019-1292-2
更新日期：2019-07-01 00:00:00
abstract：:The study of bacterial ion channels has provided fundamental insights into the structural basis of neuronal signalling; however, the native role of ion channels in bacteria has remained elusive. Here we show that ion channels conduct long-range electrical signals within bacterial biofilm communities through spatially ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature15709
更新日期：2015-11-05 00:00:00
abstract：:Comparisons of three-dimensional maps of vertebrate muscle thin filaments obtained by cryo-electron microscopy and image analysis, reveal the molecular structure of F-actin, the location of the C terminus of the monomer and the positions of the binding sites of tropomyosin, the myosin head and the N-terminal portion o...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/348217a0
更新日期：1990-11-15 00:00:00
abstract：:Many homeobox genes are clustered in a linear array along a chromosome, reflecting their ordered expression along the anterior-posterior axis of the embryo. Expression patterns as well as grafting, ectopic expression and loss-of-function experiments suggest that the Hox genes encode a combinatorial system of positiona...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/368747a0
更新日期：1994-04-21 00:00:00
abstract：:DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle, but the molecular underpinnings of their involvement, particularly in mammalian cells, remain poorly understood. Here we show that the DEAD-box RNA helicase DDX21 can sense the transcriptional status of both RNA polymerase (P...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature13923
更新日期：2015-02-12 00:00:00
abstract：:Malignancy is a common and dreaded complication following organ transplantation. The high incidence of neoplasm and its aggressive progression, which are associated with immunosuppressive therapy, are thought to be due to the resulting impairment of the organ recipient's immune-surveillance system. Here we report a me...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/17401
更新日期：1999-02-11 00:00:00
abstract：:Neural mechanisms that mediate the ability to make value-guided decisions have received substantial attention in humans and animals1-6. Experiments in animals typically involve long training periods. By contrast, choices in the real world often need to be made between new options spontaneously. It is therefore possibl...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-03115-5
更新日期：2021-01-06 00:00:00
abstract：:Cutaneous melanoma is a type of cancer with an inherent potential for lymph node colonization, which is generally preceded by neolymphangiogenesis. However, sentinel lymph node removal does not necessarily extend the overall survival of patients with melanoma. Moreover, lymphatic vessels collapse and become dysfunctio...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature22977
更新日期：2017-06-28 00:00:00
abstract：:Specific chromosomal deletions sometimes associated with tumours such as retinoblastoma (chromosome 13q14) and Wilm's tumour (chromosome 11p13) have led to the hypothesis that recessive genes may be involved in tumorigenesis. This hypothesis is supported by demonstration of allele loss specific for these regions using...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/329451a0
更新日期：1987-10-01 00:00:00
abstract：:It is known that glucose-induced depolarization of pancreatic B-cells is due to reduced membrane K+-permeability and is coupled to an increase in the rate of glycolysis, but there has been no direct evidence linking specific metabolic processes or products to the closing of membrane K+ channels. During patch-clamp stu...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/311271a0
更新日期：1984-09-20 00:00:00
abstract：:Close inbreeding is known for a variety of small mammal species for which a high probability of mortality during dispersal makes helping and delayed maturation a relatively secure fitness option. Prolonged inbreeding, however, is usually associated with lowered fitness, and it has been shown that most highly inbred sm...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/380619a0
更新日期：1996-04-18 00:00:00
abstract：:There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined approxima...
journal_title：Nature
pub_type： 杂志文章,多中心研究
doi：10.1038/nature05911
更新日期：2007-06-07 00:00:00
abstract：:The human T cell erythrocyte receptor (CD2 antigen) allows thymocytes and mature T cells to adhere to thymic epithelium and target cells through a cell surface protein, LFA-3 (refs 1-6). Monoclonal antibodies recognizing CD2 can either block adhesion or, in certain combinations, induce an antigen-independent T cell ac...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/329842a0
更新日期：1987-10-29 00:00:00
abstract：:Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision1,2. Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss; however, the generation of sensory neuronal subtypes such as photore...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-2201-4
更新日期：2020-05-01 00:00:00
abstract：:Topological states of matter are characterized by topological invariants, which are physical quantities whose values are quantized and do not depend on the details of the system (such as its shape, size and impurities). Of these quantities, the easiest to probe is the electrical Hall conductance, and fractional values...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-018-0184-1
更新日期：2018-07-01 00:00:00
abstract：:DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methylcytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and so far no base-resoluti...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature10960
更新日期：2012-03-28 00:00:00
abstract：:Nucleosomal DNA is arranged in a higher-order structure that presents a barrier to most cellular processes involving protein DNA interactions. The cellular machinery involved in sister chromatid cohesion, the cohesin complex, also requires access to the nucleosomal DNA to perform its function in chromosome segregation...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature01024
更新日期：2002-08-29 00:00:00
abstract：:The atmosphere and ionosphere of Venus have been studied in the past by spacecraft with remote sensing or in situ techniques. These early missions, however, have left us with questions about, for example, the atmospheric structure in the transition region from the upper troposphere to the lower mesosphere (50-90 km) a...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature06239
更新日期：2007-11-29 00:00:00
