Naturally Occurring Off-Switches for CRISPR-Cas9.

Abstract:

:CRISPR-Cas9 technology would be enhanced by the ability to inhibit Cas9 function spatially, temporally, or conditionally. Previously, we discovered small proteins encoded by bacteriophages that inhibit the CRISPR-Cas systems of their host bacteria. These "anti-CRISPRs" were specific to type I CRISPR-Cas systems that do not employ the Cas9 protein. We posited that nature would also yield Cas9 inhibitors in response to the evolutionary arms race between bacteriophages and their hosts. Here, we report the discovery of three distinct families of anti-CRISPRs that specifically inhibit the CRISPR-Cas9 system of Neisseria meningitidis. We show that these proteins bind directly to N. meningitidis Cas9 (NmeCas9) and can be used as potent inhibitors of genome editing by this system in human cells. These anti-CRISPR proteins now enable "off-switches" for CRISPR-Cas9 activity and provide a genetically encodable means to inhibit CRISPR-Cas9 genome editing in eukaryotes. VIDEO ABSTRACT.

journal_name

Cell

journal_title

Cell

authors

Pawluk A,Amrani N,Zhang Y,Garcia B,Hidalgo-Reyes Y,Lee J,Edraki A,Shah M,Sontheimer EJ,Maxwell KL,Davidson AR

doi

10.1016/j.cell.2016.11.017

subject

Has Abstract

pub_date

2016-12-15 00:00:00

pages

1829-1838.e9

issue

7

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(16)31589-6

journal_volume

167

pub_type

评论,杂志文章

相关文献

CELL文献大全
  • The 5' terminal structure of the methylated mRNA synthesized in vitro by vesicular stomatitis virus.

    abstract::The 5' terminal structure of the mRNA synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus in the presence of S-adenosyl-L-methione consists of 7-methyl guanosine linked to 2'-O-methyl adenosine through a 5'-5' pyrophosphate bond as m7G(5')ppp(5')A-m-p ... The alpha and beta phosp...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(75)90091-4

    authors: Abraham G,Rhodes DP,Banerjee AK

    更新日期:1975-05-01 00:00:00

  • Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter.

    abstract::The promoter specificity of transcriptional activators is generally thought to be conferred by the specificity of the DNA-binding domain, which brings the activation domain to the appropriate promoter sequence. We show here, however, that Oct-1 and Oct-2 can differentially activate transcription not through DNA bindin...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(92)90150-b

    authors: Tanaka M,Lai JS,Herr W

    更新日期:1992-02-21 00:00:00

  • Saved by the Matrix: UPR Independent Survival under ER Stress.

    abstract::Cells are protected from endoplasmic reticulum stress through the unfolded protein response (UPR). In this issue of Cell, Schinzel, Higuchi-Sanabria, Shalem et al., identify a mechanism that helps cells cope with ER stress but is independent of canonical UPR activation, instead involving the extracellular matrix hyalu...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2019.11.012

    authors: Koopman M,Hetz C,Nollen EAA

    更新日期:2019-11-27 00:00:00

  • Cellular Control of Viscosity Counters Changes in Temperature and Energy Availability.

    abstract::Cellular functioning requires the orchestration of thousands of molecular interactions in time and space. Yet most molecules in a cell move by diffusion, which is sensitive to external factors like temperature. How cells sustain complex, diffusion-based systems across wide temperature ranges is unknown. Here, we uncov...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2020.10.017

    authors: Persson LB,Ambati VS,Brandman O

    更新日期:2020-12-10 00:00:00

  • The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21.

    abstract::The neurofibromatosis type 1 (NF1) protein contains a region of significant sequence similarity to ras p21 GTPase-activating protein (GAP) and the yeast IRA1 gene product. A fragment of NF1 cDNA encoding the GAP-related domain (NF1 GRD) was expressed, immunoaffinity purified, and assayed for effects on N-ras p21 GTPas...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(90)90150-d

    authors: Martin GA,Viskochil D,Bollag G,McCabe PC,Crosier WJ,Haubruck H,Conroy L,Clark R,O'Connell P,Cawthon RM

    更新日期:1990-11-16 00:00:00

  • Oncogenic Signaling Pathways in The Cancer Genome Atlas.

    abstract::Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expressio...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2018.03.035

    authors: Sanchez-Vega F,Mina M,Armenia J,Chatila WK,Luna A,La KC,Dimitriadoy S,Liu DL,Kantheti HS,Saghafinia S,Chakravarty D,Daian F,Gao Q,Bailey MH,Liang WW,Foltz SM,Shmulevich I,Ding L,Heins Z,Ochoa A,Gross B,Gao J,Z

    更新日期:2018-04-05 00:00:00

  • A tethering complex recruits SNAREs and grabs vesicles.

    abstract::Protein tethers can bridge gaps between membranes. Ren et al. (2009) now provide evidence that the yeast Dsl1 complex tethers vesicles to the endoplasmic reticulum (ER) by binding ER SNARE proteins at its base and capturing vesicles using a loop region that extends 20 nm from the ER membrane. ...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2009.11.041

    authors: Schmitt HD,Jahn R

    更新日期:2009-12-11 00:00:00

  • Rhythmic modulation of the hematopoietic niche through neutrophil clearance.

    abstract::Unique among leukocytes, neutrophils follow daily cycles of release from and migration back into the bone marrow, where they are eliminated. Because removal of dying cells generates homeostatic signals, we explored whether neutrophil elimination triggers circadian events in the steady state. Here, we report that the h...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2013.04.040

    authors: Casanova-Acebes M,Pitaval C,Weiss LA,Nombela-Arrieta C,Chèvre R,A-González N,Kunisaki Y,Zhang D,van Rooijen N,Silberstein LE,Weber C,Nagasawa T,Frenette PS,Castrillo A,Hidalgo A

    更新日期:2013-05-23 00:00:00

  • The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats.

    abstract::I have identified an activity in crude HeLa cell extracts that satisfies the requirements for a human telomere terminal transferase or telomerase. It catalyzes the addition of a 6 nucleotide repeating pattern to oligonucleotide primers containing human or nonhuman telomeric repeat sequences. Direct sequence analyses o...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(89)90035-4

    authors: Morin GB

    更新日期:1989-11-03 00:00:00

  • Nucleotide sequence of the triosephosphate isomerase gene from Aspergillus nidulans: implications for a differential loss of introns.

    abstract::A functional cDNA from Aspergillus nidulans encoding triosephosphate isomerase (TPI) was isolated by its ability to complement a tpi1 mutation in Saccharomyces cerevisiae. This cDNA was used to obtain the corresponding gene, tpiA. Alignment of the cDNA and genomic DNA nucleotide sequences indicated that tpiA contains ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(86)90868-8

    authors: McKnight GL,O'Hara PJ,Parker ML

    更新日期:1986-07-04 00:00:00

  • Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex.

    abstract::An important signaling pathway to the actin cytoskeleton links the Rho family GTPase Cdc42 to the actin-nucleating Arp2/3 complex through N-WASP. Nevertheless, these previously identified components are not sufficient to mediate Cdc42-induced actin polymerization in a physiological context. In this paper, we describe ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2004.06.027

    authors: Ho HY,Rohatgi R,Lebensohn AM,Le Ma,Li J,Gygi SP,Kirschner MW

    更新日期:2004-07-23 00:00:00

  • Mapping human epigenomes.

    abstract::As the second dimension to the genome, the epigenome contains key information specific to every type of cells. Thousands of human epigenome maps have been produced in recent years thanks to rapid development of high throughput epigenome mapping technologies. In this review, we discuss the current epigenome mapping too...

    journal_title:Cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.cell.2013.09.011

    authors: Rivera CM,Ren B

    更新日期:2013-09-26 00:00:00

  • Rickettsia Sca4 Reduces Vinculin-Mediated Intercellular Tension to Promote Spread.

    abstract::Spotted fever group (SFG) rickettsiae are human pathogens that infect cells in the vasculature. They disseminate through host tissues by a process of cell-to-cell spread that involves protrusion formation, engulfment, and vacuolar escape. Other bacterial pathogens rely on actin-based motility to provide a physical for...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2016.09.023

    authors: Lamason RL,Bastounis E,Kafai NM,Serrano R,Del Álamo JC,Theriot JA,Welch MD

    更新日期:2016-10-20 00:00:00

  • Transcription of specific genes in isolated nuclei by exogenous RNA polymerases.

    abstract::Mouse plasmacytoma (MOPC) 460 cells contain two chromatographic forms of RNA polymerase III (IIIA and IIIB) in addition to the major class I and II RNA polymerases. Nuclei isolated from these cells actively synthesize RNA. Among the discrete transcription products observed are the 5S and 4.5S RNAs and additional low m...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(77)90028-9

    authors: Sklar VE,Roeder RG

    更新日期:1977-03-01 00:00:00

  • Drosophila ribosomal RNA genes function as an X-Y pairing site during male meiosis.

    abstract::In Drosophila melanogaster males, the sex chromosomes pair during meiosis in the centric X heterochromatin and at the base of the short arm of the Y (YS), in the vicinity of the nucleolus organizers. X chromosomes deficient for the pairing region segregate randomly from the Y. In this report we show that a single ribo...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(90)90215-z

    authors: McKee BD,Karpen GH

    更新日期:1990-04-06 00:00:00

  • p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches.

    abstract::Insertion/deletion (IDL) mismatches in DNA are lesions consisting of extra bases on one strand. Here, the binding of p53 and its 14 kDa C-terminal domain to DNAs containing one or three 3-cytosine IDL mismatches was examined. Electron microscopy showed that both p53 forms bound predominantly as tetramers at the lesion...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(05)80006-6

    authors: Lee S,Elenbaas B,Levine A,Griffith J

    更新日期:1995-06-30 00:00:00

  • Factors involved in control of tissue-specific expression of albumin gene.

    abstract::Elements controlling tissue-specific expression of the rat albumin gene reside within roughly 150 bp upstream of the transcriptional initiation site. We show here by DNAase I footprinting assays that at least four distinct factors present in extracts derived from cells expressing albumin interact with these sequences....

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(87)90036-5

    authors: Cereghini S,Raymondjean M,Carranca AG,Herbomel P,Yaniv M

    更新日期:1987-08-14 00:00:00

  • Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage.

    abstract::The mitotic checkpoint ensures proper chromosome segregation by delaying anaphase until chromosomes are aligned on the spindle. Following prolonged spindle damage, however, cells eventually exit mitosis and undergo apoptosis. We show here that a murine homolog of the yeast mitotic checkpoint gene BUB1 localizes to the...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)80255-x

    authors: Taylor SS,McKeon F

    更新日期:1997-05-30 00:00:00

  • Mitochondrial DNA synthesis in cell cycle mutants of Saccharomyces cerevisiae.

    abstract::Mitochondrial DNA replication was examined in mutants for seven different Saccharomyces cerevisiae genes which are essential for nuclear DNA replication. In cdc8 and cdc21, mutants defective in continued replication during the S phase of the cell cycle, mitochondrial DNA replication ceases at the nonpermissive tempera...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(75)90061-6

    authors: Newlon CS,Fangman WL

    更新日期:1975-08-01 00:00:00

  • Role of eukaryotic-type functional domains found in the prokaryotic enhancer receptor factor sigma 54.

    abstract::E. coli sigma 54 protein confers on promoters containing its recognition sequence the ability to be activated from distant DNA sites. Its functional domains include two leucine zipper motifs, an acidic region, and a glutamine-rich domain. Several domains were disrupted and the assembly of mutant transcription complexe...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(90)90269-k

    authors: Sasse-Dwight S,Gralla JD

    更新日期:1990-09-07 00:00:00

  • Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.

    abstract::The mutated gene responsible for the tubby obesity phenotype has been identified by positional cloning. A single base change within a splice donor site results in the incorrect retention of a single intron in the mature tub mRNA transcript. The consequence of this mutation is the substitution of the carboxy-terminal 4...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)81104-6

    authors: Kleyn PW,Fan W,Kovats SG,Lee JJ,Pulido JC,Wu Y,Berkemeier LR,Misumi DJ,Holmgren L,Charlat O,Woolf EA,Tayber O,Brody T,Shu P,Hawkins F,Kennedy B,Baldini L,Ebeling C,Alperin GD,Deeds J,Lakey ND,Culpepper J,Chen

    更新日期:1996-04-19 00:00:00

  • Multiple neuropeptides derived from a common precursor are differentially packaged and transported.

    abstract::The ELH prohormone is proteolytically processed into at least nine peptides which govern egg-laying behavior in Aplysia. Quantitative immunocytochemistry demonstrates that peptides derived from the prohormone are packaged into distinct vesicle classes. Further experiments suggest the segregation occurs via a rapid ini...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(88)91131-2

    authors: Fisher JM,Sossin W,Newcomb R,Scheller RH

    更新日期:1988-09-09 00:00:00

  • Mechanism of C. trachomatis attachment to eukaryotic host cells.

    abstract::A novel trimolecular mechanism of microbial attachment to mammalian host cells was characterized for the obligate intracellular pathogen Chlamydia trachomatis. Using purified glycosaminoglycans (GAGs) and specific GAG lyases, we demonstrated that a heparan sulfate-like GAG present on the surface of chlamydia organisms...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(92)90296-o

    authors: Zhang JP,Stephens RS

    更新日期:1992-05-29 00:00:00

  • The pie-1 and mex-1 genes and maternal control of blastomere identity in early C. elegans embryos.

    abstract::During C. elegans embryogenesis an 8-cell stage blastomere, called MS, undergoes a reproducible cleavage pattern, producing pharyngeal cells, body wall muscles, and cell deaths. We show here that maternal-effect mutations in the pie-1 and mex-1 genes cause additional 8-cell stage blastomeres to adopt a fate very simil...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(92)90542-k

    authors: Mello CC,Draper BW,Krause M,Weintraub H,Priess JR

    更新日期:1992-07-10 00:00:00

  • Phosphorylation of the human La antigen on serine 366 can regulate recycling of RNA polymerase III transcription complexes.

    abstract::The human La antigen is an RNA-binding protein that facilitates transcriptional termination and reinitiation by RNA polymerase III. Native La protein fractionates into transcriptionally active and inactive forms that are unphosphorylated and phosphorylated at serine 366, respectively, as determined by enzymatic and ma...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)81913-3

    authors: Fan H,Sakulich AL,Goodier JL,Zhang X,Qin J,Maraia RJ

    更新日期:1997-03-07 00:00:00

  • Molecular analysis of the histone gene cluster of psammechinus miliaris: II. The arrangement of the five histone-coding and spacer sequences.

    abstract::Histone DNA of Psammechinus miliaris was obtained in an enriched form by buoyant density gradient centrifugation and was cleaved into 6 kb repeat units (Birnstiel et al., 1975a) by the action of the specific endonucleases EcoRI and HindIII. Since it was suspected that the 6 kb unit harbored all five histone-coding seq...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(76)90214-2

    authors: Schaffner W,Gross K,Telford J,Birnstiel M

    更新日期:1976-08-01 00:00:00

  • Disruption of DAG1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration.

    abstract::Striated muscle-specific disruption of the dystroglycan (DAG1) gene results in loss of the dystrophin-glycoprotein complex in differentiated muscle and a remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis. We find that satellite cells, expressing dystroglycan, support continued efficient r...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(02)00907-8

    authors: Cohn RD,Henry MD,Michele DE,Barresi R,Saito F,Moore SA,Flanagan JD,Skwarchuk MW,Robbins ME,Mendell JR,Williamson RA,Campbell KP

    更新日期:2002-09-06 00:00:00

  • Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1.

    abstract::Sonic hedgehog (Shh) signaling from the posterior zone of polarizing activity (ZPA) is the primary determinant of anterior-posterior polarity in the vertebrate limb field. An active signal is produced by an autoprocessing reaction that covalently links cholesterol to the N-terminal signaling moiety (N-Shh(p)), tetheri...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(01)00369-5

    authors: Lewis PM,Dunn MP,McMahon JA,Logan M,Martin JF,St-Jacques B,McMahon AP

    更新日期:2001-06-01 00:00:00

  • Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow.

    abstract::We have used confocal videomicroscopy in real time to delineate the adhesive interactions supporting platelet thrombus formation on biologically relevant surfaces. Type I collagen fibrils exposed to flowing blood adsorb von Willebrand factor (vWF), to which platelets become initially tethered with continuous surface t...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)81607-4

    authors: Savage B,Almus-Jacobs F,Ruggeri ZM

    更新日期:1998-09-04 00:00:00

  • Reiteration frequency of the gene coding for the small subunit of ribulose--1,5--bisphosphate carboxylase.

    abstract::The messenger RNA coding for the precursor of the small subunit of ribulose--1,5--bisphosphate (Ru-P2) carboxylase has been partially purified from pea leaves. The mRNA has a size of 11.5S, is approximately 800 nucleotides long and, on cell-free translation, directs the synthesis of a single major polypeptide of 20,00...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(79)90164-8

    authors: Cashmore AR

    更新日期:1979-06-01 00:00:00