Abstract:
:Frequent codirectional collisions between the replisome and RNA polymerase (RNAP) are inevitable because the rate of replication is much faster than that of transcription. Here we show that, in E. coli, the outcome of such collisions depends on the productive state of transcription elongation complexes (ECs). Codirectional collisions with backtracked (arrested) ECs lead to DNA double-strand breaks (DSBs), whereas head-on collisions do not. A mechanistic model is proposed to explain backtracking-mediated DSBs. We further show that bacteria employ various strategies to avoid replisome collisions with backtracked RNAP, the most general of which is translation that prevents RNAP backtracking. If translation is abrogated, DSBs are suppressed by elongation factors that either prevent backtracking or reactivate backtracked ECs. Finally, termination factors also contribute to genomic stability by removing arrested ECs. Our results establish RNAP backtracking as the intrinsic hazard to chromosomal integrity and implicate active ribosomes and other anti-backtracking mechanisms in genome maintenance.
journal_name
Celljournal_title
Cellauthors
Dutta D,Shatalin K,Epshtein V,Gottesman ME,Nudler Edoi
10.1016/j.cell.2011.07.034subject
Has Abstractpub_date
2011-08-19 00:00:00pages
533-43issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(11)00848-8journal_volume
146pub_type
杂志文章相关文献
CELL文献大全abstract::Mutations in the C. elegans gene ced-3 prevent almost all programmed cell deaths, so that in a ced-3 mutant there are many extra cells. We show that the pharyngeal neuron M4 is essential for feeding in wild-type worms, but in a ced-3 mutant, one of the extra cells, probably MSpaaaaap (the sister of M4), can sometimes ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90593-9
更新日期:1987-12-24 00:00:00
abstract::Xenopus laevis oocytes respond to high temperature (greater than 31 degrees C) by the synthesis of one major (70 kilodalton) protein and by a gradual reduction in the rate of normal protein synthesis. In contrast with most other cells, the heat-shock response of Xenopus oocytes is controlled exclusively at the transla...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(82)90443-3
更新日期:1982-07-01 00:00:00
abstract::Prions have been responsible for an entire century of tragic episodes. Fifty years ago, kuru decimated the population of Papua New Guinea. Then, iatrogenic transmission of prions caused more than 250 cases of Creutzfeldt-Jakob disease. More recently, transmission of bovine spongiform encephalopathy to humans caused a ...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/s0092-8674(03)01031-6
更新日期:2004-01-23 00:00:00
abstract::Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa-animals, plants, and ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.01.024
更新日期:2017-02-23 00:00:00
abstract::Initiation of tumorigenesis in mouse skin can be accomplished by mutagenesis of the H-ras gene by treatment with chemical carcinogens. A mouse model system has been developed to study the additional genetic events that take place during tumor progression. Skin carcinomas were induced in F1 hybrid mice exhibiting restr...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(90)90523-h
更新日期:1990-05-04 00:00:00
abstract::Autophagy (literally self-eating) has diverse cytoprotective functions but also is linked to programmed cell death (PCD). In this issue, Qu et al. (2007) analyze the role of autophagy in PCD during development. Unexpectedly they find that autophagy induces apoptotic cells to present a signal to ensure their clearance,...
journal_title:Cell
pub_type: 评论,杂志文章,评审
doi:10.1016/j.cell.2007.02.023
更新日期:2007-03-09 00:00:00
abstract::The light-sensing organelle of the vertebrate rod photoreceptor, the outer segment (OS), is a modified cilium containing approximately 1,000 stacked disc membranes that are densely packed with visual pigment rhodopsin. The mammalian OS is renewed every ten days; new discs are assembled at the base of the OS by a poorl...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2007.06.030
更新日期:2007-08-10 00:00:00
abstract::Axonal transport has been intensively examined as a good model for studying the mechanism of organelle transport in cells, but it is still unclear how different types of membrane organelles are transported through the nerve axon. To elucidate the function of this mechanism, we have cloned KIF1A, a novel neuron-specifi...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90538-3
更新日期:1995-06-02 00:00:00
abstract::The physical state of the viral genome in four lines of hamster cells transformed by adenovirus type 12 (Ad12) has been investigated. The four lines of transformed cells originated from hamster cells after infection with Ad12 at multiplicities ranging from 5-350 plaque-forming units per cell. The DNA from transformed ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(77)90144-1
更新日期:1977-01-01 00:00:00
abstract::Defects in the gene encoding the endothelin-B receptor produce aganglionic megacolon and pigmentary disorders in mice and humans. We report that a targeted disruption of the mouse endothelin-3 ligand (EDN3) gene produces a similar recessive phenotype of megacolon and coat color spotting. A natural recessive mutation t...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(94)90018-3
更新日期:1994-12-30 00:00:00
abstract::Clinical trials are key to translating scientific advances into progress in cancer research and care. Confronted by developments in basic science, the landscape of clinical cancer research is rapidly evolving. Here, we review recent changes in clinical trials' design and conduct, and we forecast future directions towa...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.01.027
更新日期:2017-02-09 00:00:00
abstract::Addition of LETS glycoprotein to normal or transformed cells produces increased migration of the cells, as determined by formation of phagokinetic tracks on gold particle-coated coverslips. These tracks arise by a combination of phagocytosis of the gold particles and cellular migration. Increased motility is also evid...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(78)90129-0
更新日期:1978-06-01 00:00:00
abstract::A mechanistic description of metazoan transcription is essential for understanding the molecular processes that govern cellular decisions. To provide structural insights into the DNA recognition step of transcription initiation, we used single-particle electron microscopy (EM) to visualize human TFIID with promoter DN...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2012.12.005
更新日期:2013-01-17 00:00:00
abstract::We have isolated two adenylyl cyclase genes, designated ACA and ACG, from Dictyostelium. The proposed structure for ACA resembles that proposed for mammalian adenylyl cyclases: two large hydrophilic domains and two sets of six transmembrane spans. ACG has a novel structure, reminiscent of the membrane-bound guanylyl c...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90411-5
更新日期:1992-04-17 00:00:00
abstract::Hox homeodomain proteins are developmental regulators that determine body plan in a variety of organisms. A majority of the vertebrate Hox proteins bind DNA as heterodimers with the Pbx1 homeodomain protein. We report here the 2.35 A structure of a ternary complex containing a human HoxB1-Pbx1 heterodimer bound to DNA...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)80662-5
更新日期:1999-02-19 00:00:00
abstract::Previous work from our laboratory has demonstrated that a subclass of the aminoglycoside antibiotics, those containing the drug fragment paromamine, stimulates mistranslation in cell-free protein-synthesizing systems derived from eucaryotic cells. We report here experiments which show that the ciliate Tetrahymena ther...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(78)90201-5
更新日期:1978-02-01 00:00:00
abstract::A major problem in treatment of cancers arising in steroid-sensitive cells is their inevitable progression to a steroid-insensitive state; current therapies are based on the assumption that hormone insensitivity is associated with loss of receptor. We demonstrate for the first time that breast tumor cells can progress...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90121-8
更新日期:1987-11-20 00:00:00
abstract::Even a simple sensory stimulus can elicit distinct innate behaviors and sequences. During sensorimotor decisions, competitive interactions among neurons that promote distinct behaviors must ensure the selection and maintenance of one behavior, while suppressing others. The circuit implementation of these competitive i...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2016.09.009
更新日期:2016-10-20 00:00:00
abstract::Thrombin stimulates 32Pi incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bis-phosphate (PIP2), and phosphatidylinositol (PI), and initiates DNA synthesis in hamster (NIL) fibroblasts at a half-maximal concentration of 125 ng/ml. Neomycin, which binds PIP2 and PIP, inhibits both thro...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(85)90105-9
更新日期:1985-09-01 00:00:00
abstract::Sucrose gradient analysis of DNA isolated from detergent-pronase lysates of adult flies has been used to look for ribosomal genes not integrated into the DNA of the chromosome in genotypes containing various combinations of inversions having breakpoints in the proximal heterochromatin of the X chromosome. Unintegrated...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(77)90056-3
更新日期:1977-06-01 00:00:00
abstract::Dysregulation of splicing and alternative splicing underlies many genetic and acquired diseases. We present an overview of recent strategies and successes in modulating splicing therapeutically in clinical and preclinical contexts. Effective approaches include restoring open reading frames, influencing alternative spl...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2012.02.014
更新日期:2012-03-16 00:00:00
abstract::Many proteins (intrinsically disordered proteins, IDPs) or regions of proteins (intrinsically disordered regions, IDRs) lack a well-defined 3D structure under physiological conditions. Albeit unfolded and highly dynamic, these proteins are not denatured; rather, intrinsic structural disorder is their native, functiona...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2015.05.024
更新日期:2015-05-21 00:00:00
abstract::Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequen...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2020.11.020
更新日期:2021-01-07 00:00:00
abstract::Females but not males of the low-lymphoma RF/J strain transmit a non-Mendelian factor which suppresses the development of lymphoma in F1 crosses with mice of the high-lymphoma AKR/J strain. Suppression of lymphoma was also evident in the first backcross generation to the parental AKR strain, but only when (RF female x...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(80)90517-6
更新日期:1980-02-01 00:00:00
abstract::Discs large (DLG) mediates the clustering of synaptic molecules. Here we demonstrate that synaptic localization of DLG itself is regulated by CaMKII. We show that DLG and CaMKII colocalize at synapses and exist in the same protein complex. Constitutively activated CaMKII phenocopied structural abnormalities of dlg mut...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81964-9
更新日期:1999-08-06 00:00:00
abstract::An injection of aphidicolin into early Drosophila embryos inhibits DNA synthesis and nuclear division, while centrosome replication and many other aspects of the mitotic cycle continue. If aphidicolin is injected at nuclear cycle 7-8, the normal migration of nuclei to the embryo cortex is completely inhibited. In most...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(89)90130-x
更新日期:1989-05-19 00:00:00
abstract::Competence development and sporulation in B. subtilis are partly controlled by peptides that accumulate in culture medium as cells grow to high density. We constructed two genes that encode mature forms of two different signaling molecules, the PhrA peptide that stimulates sporulation, and CSF, the competence- and spo...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)80277-9
更新日期:1997-06-13 00:00:00
abstract::Neurotrophic factors are essential for neuronal survival and function. Recent data have demonstrated that the product of the tyrosine kinase trk proto-oncogene binds NGF and is a component of the high affinity NGF receptor. Analysis of the trkB gene product, gp145trkB, in NIH 3T3 cells indicates that this tyrosine kin...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(91)90396-g
更新日期:1991-05-31 00:00:00
abstract::In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of NPC compone...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2008.11.037
更新日期:2009-01-23 00:00:00
abstract::Compared to sperm nuclei, nuclei from adult somatic cells replicate inefficiently in frog egg extract. In this issue of Cell, Lemaitre et al. (2005) show that pre-exposure of erythrocyte nuclei to a mitotic extract removes this difference, reorganizes the chromatin into shorter loops, and allows replication at much sh...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2005.11.008
更新日期:2005-12-02 00:00:00