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https://www.readbyqxmd.com/read/29778643/inheritance-of-co-edited-genes-by-crispr-based-targeted-nucleotide-substitutions-in-rice
#1
Zenpei Shimatani, Ushio Fujikura, Hisaki Ishii, Yusuke Matsui, Minoru Suzuki, Yuki Ueke, Ken-Ichiro Taoka, Rie Terada, Keiji Nishida, Akihiko Kondo
The CRISPR/Cas9 system is a revolutionary genome-editing tool for directed gene editing in various organisms. Cas9 variants can be applied as molecular homing devices when combined with various functional effectors such as transcriptional activators or DNA modification enzymes. Target-AID is a synthetic complex of nuclease deficient Cas9 fused to an activation-induced cytidine deaminase (AID) that enables targeted nucleotide substitution (C to T or G to A). We previously demonstrated that the introduction of desired point mutations into target genes by Target-AID confers herbicide tolerance to rice callus...
April 25, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29769532/aid-apobec-like-cytidine-deaminases-are-ancient-innate-immune-mediators-in-invertebrates
#2
Mei-Chen Liu, Wen-Yun Liao, Katherine M Buckley, Shu Yuan Yang, Jonathan P Rast, Sebastian D Fugmann
In the course of both innate and adaptive immunity, cytidine deaminases within the activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) family modulate immune responses by mutating specific nucleic acid sequences of hosts and pathogens. The evolutionary emergence of these mediators, however, seems to coincide precisely with the emergence of adaptive immunity in vertebrates. Here, we show a family of genes in species within two divergent invertebrate phyla-the echinoderm Strongylocentrotus purpuratus and the brachiopod Lingula anatina-that encode proteins with similarities in amino acid sequence and enzymatic activities to the vertebrate AID/APOBECs...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29744038/generating-and-repairing-genetically-programmed-dna-breaks-during-immunoglobulin-class-switch-recombination
#3
REVIEW
Laura Nicolas, Montserrat Cols, Jee Eun Choi, Jayanta Chaudhuri, Bao Vuong
Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR...
2018: F1000Research
https://www.readbyqxmd.com/read/29743315/an-unmutated-igm-response-to-the-vi-polysaccharide-of-salmonella-typhi-contributes-to-protective-immunity-in-a-murine-model-of-typhoid
#4
Kalgi D Pandya, Isabel Palomo-Caturla, Justin A Walker, Vijay K Sandilya, Zhijiu Zhong, Kishore R Alugupalli
T cell-dependent B cell responses typically develop in germinal centers. Abs generated during such responses are isotype switched and have a high affinity to the Ag because of somatic hypermutation of Ab genes. B cell responses to purified polysaccharides are T cell independent and do not result in the formation of bona fide germinal centers, and the dominant Ab isotype produced during such responses is IgM with very few or no somatic mutations. Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and Ig isotype switching in humans and mice...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29735400/concept-of-dna-lesion-longevity-and-chromosomal-translocations
#5
REVIEW
Nicholas R Pannunzio, Michael R Lieber
A subset of chromosomal translocations related to B cell malignancy in human patients arises due to DNA breaks occurring within defined 20-600 base pair (bp) zones. Several factors influence the breakage rate at these sites including transcription, DNA sequence, and topological tension. These factors favor non-B DNA structures that permit formation of transient single-stranded DNA (ssDNA), making the DNA more vulnerable to agents such as the enzyme activation-induced cytidine deaminase (AID) and reactive oxygen species (ROS)...
May 4, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29731414/rna-helicase-ddx1-converts-rna-g-quadruplex-structures-into-r-loops-to-promote-igh-class-switch-recombination
#6
Claudia Ribeiro de Almeida, Somdutta Dhir, Ashish Dhir, Amin E Moghaddam, Quentin Sattentau, Anton Meinhart, Nicholas J Proudfoot
Class switch recombination (CSR) at the immunoglobulin heavy-chain (IgH) locus is associated with the formation of R-loop structures over switch (S) regions. While these often occur co-transcriptionally between nascent RNA and template DNA, we now show that they also form as part of a post-transcriptional mechanism targeting AID to IgH S-regions. This depends on the RNA helicase DDX1 that is also required for CSR in vivo. DDX1 binds to G-quadruplex (G4) structures present in intronic switch transcripts and converts them into S-region R-loops...
April 30, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29728506/abrogation-of-lupus-nephritis-in-somatic-hypermutation-deficient-mrl-lpr-mice
#7
Fengqi Hao, Miaomiao Tian, Yunpeng Feng, Chao Quan, Yixi Chen, Shuai Chen, Min Wei
Systemic lupus erythematosus (SLE) is an autoimmune disease posing threats to multiple organs in the human body. As a typical manifestation of SLE, lupus nephritis is characterized by a series of pathological changes in glomerulus as well as accumulation of pathogenic autoreactive IgG with complement in the kidney that dramatically disrupts renal functions. Activation-induced deaminase (AID), which governs both somatic hypermutation (SHM) and class-switch recombination (CSR), has been shown to be essential for the regulation of SLE...
May 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29716522/the-cytidine-deaminase-under-representation-reporter-cdur-as-a-tool-to-study-evolution-of-sequences-under-deaminase-mutational-pressure
#8
Maxwell Shapiro, Stephen Meier, Thomas MacCarthy
BACKGROUND: Activation induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) are deaminases that mutate C to U on single-stranded DNA (ssDNA). AID is expressed primarily in germinal center B-cells, where it facilitates affinity maturation and class-switch recombination. APOBEC3 are a family of anti-viral proteins that act as part of the intrinsic immune response. In both cases, there are particular sequence motifs, also known as "mutation motifs", to which these deaminases prefer to bind and mutate...
May 2, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29704159/diversity-of-immunoglobulin-ig-isotypes-and-the-role-of-activation-induced-cytidine-deaminase-aid-in-fish
#9
REVIEW
Bhakti Patel, Rajanya Banerjee, Mrinal Samanta, Surajit Das
The disparate diversity in immunoglobulin (Ig) repertoire has been a subject of fascination since the emergence of prototypic adaptive immune system in vertebrates. The carboxy terminus region of activation-induced cytidine deaminase (AID) has been well established in tetrapod lineage and is crucial for its function in class switch recombination (CSR) event of Ig diversification. The absence of CSR in the paraphyletic group of fish is probably due to changes in catalytic domain of AID and lack of cis-elements in IgH locus...
April 27, 2018: Molecular Biotechnology
https://www.readbyqxmd.com/read/29669924/samhd1-enhances-immunoglobulin-hypermutation-by-promoting-transversion-mutation
#10
Eddy Sanchai Thientosapol, Daniel Bosnjak, Timothy Durack, Igor Stevanovski, Michelle van Geldermalsen, Jeff Holst, Zeenat Jahan, Caitlin Shepard, Wolfgang Weninger, Baek Kim, Robert Brink, Christopher J Jolly
Activation-induced deaminase (AID) initiates hypermutation of Ig genes in activated B cells by converting C:G into U:G base pairs. G1 -phase variants of uracil base excision repair (BER) and mismatch repair (MMR) then deploy translesion polymerases including REV1 and Pol η, which exacerbates mutation. dNTP paucity may contribute to hypermutation, because dNTP levels are reduced in G1 phase to inhibit viral replication. To derestrict G1 -phase dNTP supply, we CRISPR-inactivated SAMHD1 (which degrades dNTPs) in germinal center B cells...
April 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666292/human-immunodeficiency-virus-tat-protein-aids-v-region-somatic-hypermutation-in-human-b-cells
#11
Xiaohua Wang, Zhi Duan, Guojun Yu, Manxia Fan, Matthew D Scharff
Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggested by the extraordinary high frequency of mutation, insertion, and deletion in the broadly neutralizing HIV antibodies. Since HIV does not infect B cells, the molecular mechanisms of this genomic instability remain to be fully defined...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29665088/gain-of-function-analysis-of-cis-acting-diversification-elements-in-dt40-cells
#12
Randolph B Caldwell, Herbert Braselmann, Steffen Heuer, Ulrike Schötz, Horst Zitzelsberger
Activation-induced cytidine deaminase (AID) is required for the immunoglobulin diversification processes of somatic hypermutation, gene conversion and class-switch recombination. The targeting of AID's deamination activity is thought to be a combination of cis- and trans-acting elements, but has not been fully elucidated. Deletion analysis of putative proximal cis-regulatory motifs, while helpful, fails to identify additive versus cumulative effects, redundancy, and may create new motifs where none previously existed...
April 17, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29664399/somatic-hypermutation-of-t-cell-receptor-%C3%AE-chain-contributes-to-selection-in-nurse-shark-thymus
#13
Jeannine A Ott, Caitlin D Castro, Thaddeus C Deiss, Yuko Ohta, Martin F Flajnik, Michael F Criscitiello
Since the discovery of the T cell receptor (TcR), immunologists have assigned somatic hypermutation (SHM) as a mechanism employed solely by B cells to diversify their antigen receptors. Remarkably, we found SHM acting in the thymus on α chain locus of shark TcR. SHM in developing shark T cells likely is catalyzed by activation-induced cytidine deaminase (AID) and results in both point and tandem mutations that accumulate non-conservative amino acid replacements within complementarity-determining regions (CDRs)...
April 17, 2018: ELife
https://www.readbyqxmd.com/read/29625296/j-h-6-downstream-intronic-sequence-is-dispensable-for-rna-polymerase-ii-accumulation-and-somatic-hypermutation-of-the-variable-gene-in-ramos-cells
#14
Diana P Castiblanco, Darrell D Norton, Robert W Maul, Patricia J Gearhart
Activation-induced deaminase (AID) introduces nucleotide substitutions within the variable region of immunoglobulin genes to promote antibody diversity. This activity, which is limited to 1.5 kb downstream of the variable gene promoter, mutates both the coding exon and downstream intronic sequences. We recently reported that RNA polymerase II accumulates in these regions during transcription in mice. This build-up directly correlates with the area that is accessible to AID, and manipulation of RNA polymerase II levels alters the mutation frequency...
April 3, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29618650/siv-mac239-vif-and-human-apobec3b-interactions-resemble-those-between-hiv-1-vif-and-human-apobec3g
#15
Jiayi Wang, Nadine M Shaban, Allison M Land, William L Brown, Reuben S Harris
Several members of the APOBEC3 DNA cytosine deaminase family can potently inhibit Vif-deficient HIV-1 by catalyzing cytosine deamination in viral cDNA and impeding reverse transcription. HIV-1 counteracts restriction with the virally encoded Vif protein, which targets relevant APOBEC3 proteins for proteasomal degradation. HIV-1 Vif is optimized for degrading the restrictive human APOBEC3 repertoire and, in general, lentiviral Vif proteins specifically target the restricting APOBEC3 enzymes of each host species...
April 4, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29593215/a-licensing-step-links-aid-to-transcription-elongation-for-mutagenesis-in-b-cells
#16
Stephen P Methot, Ludivine C Litzler, Poorani Ganesh Subramani, Anil K Eranki, Heather Fifield, Anne-Marie Patenaude, Julian C Gilmore, Gabriel E Santiago, Halil Bagci, Jean-François Côté, Mani Larijani, Ramiro E Verdun, Javier M Di Noia
Activation-induced deaminase (AID) mutates the immunoglobulin (Ig) genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B cells, thus underpinning antibody responses. AID mutates a few hundred other loci, but most AID-occupied genes are spared. The mechanisms underlying productive deamination versus non-productive AID targeting are unclear. Here we show that three clustered arginine residues define a functional AID domain required for SHM, CSR, and off-target activity in B cells without affecting AID deaminase activity or Escherichia coli mutagenesis...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29581109/b-cell-tumor-development-in-tet2-deficient-mice
#17
Enguerran Mouly, Hussein Ghamlouch, Veronique Della-Valle, Laurianne Scourzic, Cyril Quivoron, Damien Roos-Weil, Patrycja Pawlikowska, Véronique Saada, M'Boyba K Diop, Cécile K Lopez, Michaela Fontenay, Philippe Dessen, Ivo P Touw, Thomas Mercher, Said Aoufouchi, Olivier A Bernard
The TET2 gene encodes an α-ketoglutarate-dependent dioxygenase able to oxidize 5-methylcytosine into 5-hydroxymethylcytosine, which is a step toward active DNA demethylation. TET2 is frequently mutated in myeloid malignancies but also in B- and T-cell malignancies. TET2 somatic mutations are also identified in healthy elderly individuals with clonal hematopoiesis. Tet2 -deficient mouse models showed widespread hematological differentiation abnormalities, including myeloid, T-cell, and B-cell malignancies. We show here that, similar to what is observed with constitutive Tet2 -deficient mice, B-cell-specific Tet2 knockout leads to abnormalities in the B1-cell subset and a development of B-cell malignancies after long latency...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29580925/macbeth-multiplex-automated-corynebacterium-glutamicum-base-editing-method
#18
Yu Wang, Ye Liu, Jiao Liu, Yanmei Guo, Liwen Fan, Xiaomeng Ni, Xiaomei Zheng, Meng Wang, Ping Zheng, Jibin Sun, Yanhe Ma
CRISPR/Cas9 or Cpf1-introduced double strand break dramatically decreases bacterial cell survival rate, which hampers multiplex genome editing in bacteria. In addition, the requirement of a foreign DNA template for each target locus is labor demanding and may encounter more GMO related regulatory hurdle in industrial applications. Herein, we developed a multiplex automated Corynebacterium glutamicum base editing method (MACBETH) using CRISPR/Cas9 and activation-induced cytidine deaminase (AID), without foreign DNA templates, achieving single-, double-, and triple-locus editing with efficiencies up to 100%, 87...
March 24, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29555777/expansions-diversification-and-interindividual-copy-number-variations-of-aid-apobec-family-cytidine-deaminase-genes-in-lampreys
#19
Stephen J Holland, Lesley M Berghuis, Justin J King, Lakshminarayan M Iyer, Katarzyna Sikora, Heather Fifield, Sarah Peter, Emma M Quinlan, Fumiaki Sugahara, Prashant Shingate, Inês Trancoso, Norimasa Iwanami, Elena Temereva, Christine Strohmeier, Shigeru Kuratani, Byrappa Venkatesh, Guillaume Evanno, L Aravind, Michael Schorpp, Mani Larijani, Thomas Boehm
Cytidine deaminases of the AID/APOBEC family catalyze C-to-U nucleotide transitions in mRNA or DNA. Members of the APOBEC3 branch are involved in antiviral defense, whereas AID contributes to diversification of antibody repertoires in jawed vertebrates via somatic hypermutation, gene conversion, and class switch recombination. In the extant jawless vertebrate, the lamprey, two members of the AID/APOBEC family are implicated in the generation of somatic diversity of the variable lymphocyte receptors (VLRs). Expression studies linked CDA1 and CDA2 genes to the assembly of VLRA /C genes in T-like cells and the VLRB genes in B-like cells, respectively...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29555751/diversification-of-aid-apobec-like-deaminases-in-metazoa-multiplicity-of-clades-and-widespread-roles-in-immunity
#20
Arunkumar Krishnan, Lakshminarayan M Iyer, Stephen J Holland, Thomas Boehm, L Aravind
AID/APOBEC deaminases (AADs) convert cytidine to uridine in single-stranded nucleic acids. They are involved in numerous mutagenic processes, including those underpinning vertebrate innate and adaptive immunity. Using a multipronged sequence analysis strategy, we uncover several AADs across metazoa, dictyosteliida, and algae, including multiple previously unreported vertebrate clades, and versions from urochordates, nematodes, echinoderms, arthropods, lophotrochozoans, cnidarians, and porifera. Evolutionary analysis suggests a fundamental division of AADs early in metazoan evolution into secreted deaminases (SNADs) and classical AADs, followed by diversification into several clades driven by rapid-sequence evolution, gene loss, lineage-specific expansions, and lateral transfer to various algae...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
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