当前位置： SCI文献检索 > NUCLEIC ACIDS RESEARCH期刊下所有文献 > Decoding non-random mutational signatures at Cas9 targeted sites.

Decoding non-random mutational signatures at Cas9 targeted sites.

Abstract：

:The mutation patterns at Cas9 targeted sites contain unique information regarding the nuclease activity and repair mechanisms in mammalian cells. However, analytical framework for extracting such information are lacking. Here, we present a novel computational platform called Rational InDel Meta-Analysis (RIMA) that enables an in-depth comprehensive analysis of Cas9-induced genetic alterations, especially InDels mutations. RIMA can be used to quantitate the contribution of classical microhomology-mediated end joining (c-MMEJ) pathway in the formation of mutations at Cas9 target sites. We used RIMA to compare mutational signatures at 15 independent Cas9 target sites in human A549 wildtype and A549-POLQ knockout cells to elucidate the role of DNA polymerase θ in c-MMEJ. Moreover, the single nucleotide insertions at the Cas9 target sites represent duplications of preceding nucleotides, suggesting that the flexibility of the Cas9 nuclease domains results in both blunt- and staggered-end cuts. Thymine at the fourth nucleotide before protospacer adjacent motif (PAM) results in a two-fold higher occurrence of single nucleotide InDels compared to guanine at the same position. This study provides a novel approach for the characterization of the Cas9 nucleases with improved accuracy in predicting genome editing outcomes and a potential strategy for homology-independent targeted genomic integration.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Taheri-Ghahfarokhi A,Taylor BJM,Nitsch R,Lundin A,Cavallo AL,Madeyski-Bengtson K,Karlsson F,Clausen M,Hicks R,Mayr LM,Bohlooly-Y M,Maresca M

doi

10.1093/nar/gky653

subject

Has Abstract

pub_date

2018-09-19 00:00:00

pages

8417-8434

issue

16

eissn

0305-1048

issn

1362-4962

pii

5055824

journal_volume

46

pub_type

杂志文章

相关文献

NUCLEIC ACIDS RESEARCH文献大全
  • Change of RNase P RNA function by single base mutation correlates with perturbation of metal ion binding in P4 as determined by NMR spectroscopy.

    abstract：:The solution structures of two 27 nt RNA hairpins and their complexes with cobalt(III)-hexammine [Co(NH(3))(6)(3+)] were determined by NMR spectroscopy. The RNA hairpins are variants of the P4 region from Escherichia coli RNase P RNA: a U-to-A mutant changing the identity of the bulged nucleotide, and a U-to-C, C-to-U...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkh961

    authors： Schmitz M

    更新日期：2004-12-02 00:00:00

  • Monitoring of chromatin organization in live cells by FRIC. Effects of the inner nuclear membrane protein Samp1.

    abstract：:In most cells, transcriptionally inactive heterochromatin is preferentially localized in the nuclear periphery and transcriptionally active euchromatin is localized in the nuclear interior. Different cell types display characteristic chromatin distribution patterns, which change dramatically during cell differentiatio...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkz123

    authors： Bergqvist C,Niss F,Figueroa RA,Beckman M,Maksel D,Jafferali MH,Kulyté A,Ström AL,Hallberg E

    更新日期：2019-05-21 00:00:00

  • Use of structural DNA properties for the prediction of transcription-factor binding sites in Escherichia coli.

    abstract：:Recognition of genomic binding sites by transcription factors can occur through base-specific recognition, or by recognition of variations within the structure of the DNA macromolecule. In this article, we investigate what information can be retrieved from local DNA structural properties that is relevant to transcript...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkq1071

    authors： Meysman P,Dang TH,Laukens K,De Smet R,Wu Y,Marchal K,Engelen K

    更新日期：2011-01-01 00:00:00

  • Qgrid: clustering tool for detecting charged and hydrophobic regions in proteins.

    abstract：:We have developed a simple but powerful method and web server to quickly locate charged and hydrophobic clusters in proteins (http://www.netasa.org/qgrid/index.html). For the charged clusters, each atom in the protein is first assigned a charge according to a standard force field. Then a box is created with dimensions...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkh363

    authors： Ahmad S,Sarai A

    更新日期：2004-07-01 00:00:00

  • Cloning and characterization of the MboII restriction-modification system.

    abstract：:The two genes encoding the class IIS restriction-modification system MboII from Moraxella bovis were cloned separately in two compatible plasmids and expressed in E. coli RR1 delta M15. The nucleotide sequences of the MboII endonuclease (R.MboII) and methylase (M.MboII) genes were determined and the putative start cod...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/19.5.1007

    authors： Bocklage H,Heeger K,Müller-Hill B

    更新日期：1991-03-11 00:00:00

  • Regulated processive transcription of chromatin by T7 RNA polymerase in Trypanosoma brucei.

    abstract：:Inability of T7 RNA polymerase to processively transcribe higher eukaryotic chromatin is interpreted as a correlate of its reported inhibition by nucleosomes on reconstituted templates in vitro . We used chromosomally integrated reporter cassettes to examine features of T7 transcription in a lower eukaryotic system. L...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/26.20.4626

    authors： Wirtz E,Hoek M,Cross GA

    更新日期：1998-10-15 00:00:00

  • A comparative database of group I intron structures.

    abstract：:We have created a database of comparatively derived group I intron secondary structure diagrams. This collection currently contains a broad sampling of phylogenetically and structurally similar and diverse structures from over 200 publicly available intron sequences. As more group I introns are sequenced and added to ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/22.17.3508

    authors： Damberger SH,Gutell RR

    更新日期：1994-09-01 00:00:00

  • Differential transcription of the orphan receptor RORbeta in nuclear extracts derived from Neuro2A and HeLa cells.

    abstract：:An important model system for studying the process leading to productive transcription is provided by the superfamily of nuclear receptors, which are for the most part ligand-controlled transcription factors. Over the past years several 'orphan' nuclear receptors have been isolated for which no ligand has yet been ide...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/29.16.3424

    authors： Gawlas K,Stunnenberg HG

    更新日期：2001-08-15 00:00:00

  • Topoisomerase II, scaffold component, promotes chromatin compaction in vitro in a linker-histone H1-dependent manner.

    abstract：:TopoisomeraseII (Topo II) is a major component of chromosomal scaffolds and essential for mitotic chromosome condensation, but the mechanism of this action remains unknown. Here, we used an in vitro chromatin reconstitution system in combination with atomic force and fluorescence microscopic analyses to determine how ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkm116

    authors： Hizume K,Araki S,Yoshikawa K,Takeyasu K

    更新日期：2007-01-01 00:00:00

  • Chemical synthesis of a gene for somatomedin C.

    abstract：:A synthetic gene for somatomedin C, a human growth factor, has been assembled by a single ligation of 23 oligodeoxyribonucleotides, which were chemically synthesized by an improved solid phase phosphotriester method. ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/13.8.2959

    authors： Sproat BS,Gait MJ

    更新日期：1985-04-25 00:00:00

  • Genome maintenance in Saccharomyces cerevisiae: the role of SUMO and SUMO-targeted ubiquitin ligases.

    abstract：:The genome of the cell is often exposed to DNA damaging agents and therefore requires an intricate well-regulated DNA damage response (DDR) to overcome its deleterious effects. The DDR needs proper regulation for its timely activation, repression, as well as appropriate choice of repair pathway. Studies in Saccharomyc...

    journal_title：Nucleic acids research

    pub_type： 杂志文章,评审

    doi：10.1093/nar/gkw1369

    authors： Jalal D,Chalissery J,Hassan AH

    更新日期：2017-03-17 00:00:00

  • Mapping the LINE1 ORF1 protein interactome reveals associated inhibitors of human retrotransposition.

    abstract：:LINE1s occupy 17% of the human genome and are its only active autonomous mobile DNA. L1s are also responsible for genomic insertion of processed pseudogenes and >1 million non-autonomous retrotransposons (Alus and SVAs). These elements have significant effects on gene organization and expression. Despite the importanc...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkt512

    authors： Goodier JL,Cheung LE,Kazazian HH Jr

    更新日期：2013-08-01 00:00:00

  • Long non-coding RNAs function annotation: a global prediction method based on bi-colored networks.

    abstract：:More and more evidences demonstrate that the long non-coding RNAs (lncRNAs) play many key roles in diverse biological processes. There is a critical need to annotate the functions of increasing available lncRNAs. In this article, we try to apply a global network-based strategy to tackle this issue for the first time. ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gks967

    authors： Guo X,Gao L,Liao Q,Xiao H,Ma X,Yang X,Luo H,Zhao G,Bu D,Jiao F,Shao Q,Chen R,Zhao Y

    更新日期：2013-01-01 00:00:00

  • The mouse genome database: genotypes, phenotypes, and models of human disease.

    abstract：:The laboratory mouse is the premier animal model for studying human biology because all life stages can be accessed experimentally, a completely sequenced reference genome is publicly available and there exists a myriad of genomic tools for comparative and experimental research. In the current era of genome scale, dat...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gks1115

    authors： Bult CJ,Eppig JT,Blake JA,Kadin JA,Richardson JE,Mouse Genome Database Group.

    更新日期：2013-01-01 00:00:00

  • Structure and evolution of a mouse tRNA gene cluster encoding tRNAAsp, tRNAGly and tRNAGlu and an unlinked, solitary gene encoding tRNAAsp.

    abstract：:We have sequenced mouse tRNA genes from two recombinant lambda phage. An 1800 bp sequence from one phage contains 3 tRNA genes, potentially encoding tRNAAsp, tRNAGly, and tRNAGlu, separated by spacer sequences of 587 bp and 436 bp, respectively. The mouse tRNA gene cluster is homologous to a rat sequence (Sekiya et al...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/11.24.8761

    authors： Looney JE,Harding JD

    更新日期：1983-12-20 00:00:00

  • A new method of representing DNA sequences which combines ease of visual analysis with machine readability.

    abstract：:A new method of representing DNA sequences has been devised which is termed stave projection. Compared with other formats for showing the base sequences of DNA, this method greatly enhances the ease of visual analysis of the sequences of bases and it is also in a machine readable form. Using this method it is possible...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/14.1.509

    authors： Cowin JE,Jellis CH,Rickwood D

    更新日期：1986-01-10 00:00:00

  • Pathbase: a database of mutant mouse pathology.

    abstract：:Pathbase is a database that stores images of the abnormal histology associated with spontaneous and induced mutations of both embryonic and adult mice including those produced by transgenesis, targeted mutagenesis and chemical mutagenesis. Images of normal mouse histology and strain-dependent background lesions are al...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkh124

    authors： Schofield PN,Bard JB,Booth C,Boniver J,Covelli V,Delvenne P,Ellender M,Engstrom W,Goessner W,Gruenberger M,Hoefler H,Hopewell J,Mancuso M,Mothersill C,Potten CS,Quintanilla-Fend L,Rozell B,Sariola H,Sundberg JP,Ward

    更新日期：2004-01-01 00:00:00

  • A comparison of the different DNA binding specificities of the bZip proteins C/EBP and GCN4.

    abstract：:The bZip proteins GCN4 and C/EBP differ in their DNA binding specificities: GCN4 binds well to the pseudopalindromic AP1 site 5'-A4T3G2A1C0T1C2'A3'T4'-3' and to the palindromic ATF/CREB sequence 5'-A4T3G2A1-C0*G0'T1'C2'A3'T4'-3'; C/EBP preferentially recognizes the palindromic sequence 5'-A4T3T2G1C0*G0'C1'A2'-A3'T4'-3...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/23.20.4162

    authors： Koldin B,Suckow M,Seydel A,von Wilcken-Bergmann B,Müller-Hill B

    更新日期：1995-10-25 00:00:00

  • Influence of flanking sequences on variability in expression levels of an introduced gene in transgenic tobacco plants.

    abstract：:The petunia rbcS gene SSU301 was introduced into tobacco using Agrobacterium tumefaciens-mediated transformation. The time at which rbcS expression was maximal after transfer of the tobacco plants to the greenhouse was determined. The expression level of the SSU301 gene varied up to 9 fold between individual tobacco p...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/16.19.9267

    authors： Dean C,Jones J,Favreau M,Dunsmuir P,Bedbrook J

    更新日期：1988-10-11 00:00:00

  • A novel, single plasmid, approach to in-frame fusion.

    abstract：:The sequence GCGCGCGCGC contains three overlapping, mutually exclusive, BssHII restriction sites, each corresponding to one of the three different reading frames. When inserted into a plasmid and digested with BssHII, the three sites in this sequence are cleaved at an approximate ratio of 2:1:2. Consequently, this sys...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/17.8.3107

    authors： Orum H,Poulsen LK

    更新日期：1989-04-25 00:00:00

  • NGS-based identification and tracing of microsatellite instability from minute amounts DNA using inter-Alu-PCR.

    abstract：:Sensitive detection of microsatellite instability (MSI) in tissue or liquid biopsies using next generation sequencing (NGS) has growing prognostic and predictive applications in cancer. However, the complexities of NGS make it cumbersome as compared to established multiplex-PCR detection of MSI. We present a new appro...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkaa1175

    authors： Yu F,Leong KW,Makrigiorgos A,Adalsteinsson VA,Ladas I,Ng K,Mamon H,Makrigiorgos GM

    更新日期：2020-12-08 00:00:00

  • Does the HIV-1 primer activation signal interact with tRNA3(Lys) during the initiation of reverse transcription?

    abstract：:Reverse transcription of HIV-1 RNA is primed by a tRNA3(Lys) molecule bound at the primer binding site (PBS). Complex intermolecular interactions were proposed between tRNA3(Lys) and the RNA of the HIV-1 Mal isolate. Recently, an alternative interaction was proposed between the TPsiC stem of tRNA3(Lys) and a primer ac...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkg187

    authors： Goldschmidt V,Ehresmann C,Ehresmann B,Marquet R

    更新日期：2003-02-01 00:00:00

  • Database resources of the National Center for Biotechnology Information.

    abstract：:The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. The Entrez system provides search and re...

    journal_title：Nucleic acids research

    pub_type： 杂志文章,评审

    doi：10.1093/nar/gkaa892

    authors： Sayers EW,Beck J,Bolton EE,Bourexis D,Brister JR,Canese K,Comeau DC,Funk K,Kim S,Klimke W,Marchler-Bauer A,Landrum M,Lathrop S,Lu Z,Madden TL,O'Leary N,Phan L,Rangwala SH,Schneider VA,Skripchenko Y,Wang J,Ye J,

    更新日期：2021-01-08 00:00:00

  • NPGPx modulates CPEB2-controlled HIF-1α RNA translation in response to oxidative stress.

    abstract：:Non-selenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx or GPx7) is an oxidative stress sensor that modulates the antioxidative activity of its target proteins through intermolecular disulfide bond formation. Given NPGPx's role in protecting cells from oxidative damage, identification of...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkv1010

    authors： Chen PJ,Weng JY,Hsu PH,Shew JY,Huang YS,Lee WH

    更新日期：2015-10-30 00:00:00

  • Biochemical and electron microscope analyses of the DNA reverse transcripts present in the virus-like particles of the yeast transposon Ty1. Identification of a second origin of Ty1DNA plus strand synthesis.

    abstract：:Transposition of Saccharomyces cerevisiae Ty1 retroelements has been shown to involve reverse transcription in intracytoplasmic virus-like particles (Ty-VLPs). Ty DNA present in the particles specified by Ty1-H3 element was found to consist of the full-length genomic DNA as well as incomplete cDNAs mainly of plus pola...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/21.15.3513

    authors： Pochart P,Agoutin B,Rousset S,Chanet R,Doroszkiewicz V,Heyman T

    更新日期：1993-07-25 00:00:00

  • Inducible model for beta-six-mediated site-specific recombination in mammalian cells.

    abstract：:The prokaryotic beta recombinase catalyzes site-specific recombination between two directly oriented minimal six sites in chromatin-integrated substrates. Here, we demonstrate that an enhanced green fluorescent protein (EGFP)-fused version of beta recombinase (beta-EGFP) is fully active, retaining most specific activi...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gnj001

    authors： Servert P,Garcia-Castro J,Díaz V,Lucas D,Gonzalez MA,Martínez-A C,Bernad A

    更新日期：2006-01-03 00:00:00

  • Representation of unique sequences in libraries of randomized nucleic acids.

    abstract：:From a library of nucleic acid molecules, which are randomized in parts of their sequence, unique sequence variants can be selected for specific properties. The planning of such an in vitro selection experiment requires some consideration regarding how much DNA template or RNA transcript should be used initially. The ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/24.17.3437

    authors： Tabler M,Benos P,Dörr M

    更新日期：1996-09-01 00:00:00

  • Repeat 1 of TAL effectors affects target specificity for the base at position zero.

    abstract：:AvrBs3, the founding member of the Xanthomonas transcription-activator-like effectors (TALEs), is translocated into the plant cell where it localizes to the nucleus and acts as transcription factor. The DNA-binding domain of AvrBs3 consists of 17.5 nearly-identical 34 amino acid-repeats. Each repeat specifies binding ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gku341

    authors： Schreiber T,Bonas U

    更新日期：2014-06-01 00:00:00

  • The elongation factor 1 A-2 isoform from rabbit: cloning of the cDNA and characterization of the protein.

    abstract：:Eukaryotic elongation factor 1 A (eEF1A, formerly elongation factor-1 alpha) is an important component of the protein synthesis apparatus. Here we report the isolation and characterization of the cDNA sequence encoding rabbit eEF1A-2, an isoform of eEF1A, as well as a structural and functional comparison of the two ra...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/26.8.1884

    authors： Kahns S,Lund A,Kristensen P,Knudsen CR,Clark BF,Cavallius J,Merrick WC

    更新日期：1998-04-15 00:00:00

  • Different binding site requirements for binding and activation for the bipartite enhancer factor EF-1A.

    abstract：:The human transcription factor EF-1A binds to the purine-rich E1A core enhancer sequence in the adenovirus E1A and E4 and polyomavirus enhancer regions. The consensus binding site for EF-1A resembles that of members of the ets domain protein family. EF-1A activation of transcription requires a dimeric binding site. An...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/20.24.6555

    authors： Bolwig GM,Bruder JT,Hearing P

    更新日期：1992-12-25 00:00:00