Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
FEBS J
2017 Jun 01;28411:1590-1605. doi: 10.1111/febs.13990.
Show Gene links
Show Anatomy links
New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination.
Carmona LM
,
Schatz DG
.
???displayArticle.abstract???
The adaptive immune system of jawed vertebrates relies on V(D)J recombination as one of the main processes to generate the diverse array of receptors necessary for the recognition of a wide range of pathogens. The DNA cleavage reaction necessary for the assembly of the antigen receptor genes from an array of potential gene segments is mediated by the recombination-activating gene proteins RAG1 and RAG2. The RAG proteins have been proposed to originate from a transposable element (TE) as they share mechanistic and structural similarities with several families of transposases and are themselves capable of mediating transposition. A number of RAG-like proteins and TEs with sequence similarity to RAG1 and RAG2 have been identified, but only recently has their function begun to be characterized, revealing mechanistic links to the vertebrate RAGs. Of particular significance is the discovery of ProtoRAG, a transposon superfamily found in the genome of the basal chordate amphioxus. ProtoRAG has many of the sequence and mechanistic features predicted for the ancestral RAG transposon and is likely to be an evolutionary relative of RAG1 and RAG2. In addition, early observations suggesting that RAG1 is able to mediate V(D)J recombination in the absence of RAG2 have been confirmed, implying independent evolutionary origins for the two RAG genes. Here, recent progress in identifying and characterizing RAG-like proteins and the TEs that encode them is summarized and a refined model for the evolution of V(D)J recombination and the RAG proteins is presented.
Agrawal,
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system.
1998, Pubmed
Agrawal,
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system.
1998,
Pubmed
Azumi,
Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: "waiting for Godot".
2003,
Pubmed
Bellon,
Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster.
1997,
Pubmed
Bhasin,
Hairpin formation in Tn5 transposition.
1999,
Pubmed
Callebaut,
The V(D)J recombination activating protein RAG2 consists of a six-bladed propeller and a PHD fingerlike domain, as revealed by sequence analysis.
1998,
Pubmed
Carmona,
Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination.
2016,
Pubmed
,
Echinobase
Chatterji,
Mobilization of RAG-generated signal ends by transposition and insertion in vivo.
2006,
Pubmed
Conticello,
Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases.
2005,
Pubmed
Corneo,
Rag mutations reveal robust alternative end joining.
2007,
Pubmed
Coster,
A dual interaction between the DNA damage response protein MDC1 and the RAG1 subunit of the V(D)J recombinase.
2012,
Pubmed
Cui,
Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway.
2007,
Pubmed
Curry,
Chromosomal reinsertion of broken RSS ends during T cell development.
2007,
Pubmed
Dehal,
The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins.
2002,
Pubmed
Dreyfus,
Paleo-immunology: evidence consistent with insertion of a primordial herpes virus-like element in the origins of acquired immunity.
2009,
Pubmed
,
Echinobase
Dudley,
Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice.
2003,
Pubmed
Elkin,
The C-terminal portion of RAG2 protects against transposition in vitro.
2003,
Pubmed
Flajnik,
Re-evaluation of the immunological Big Bang.
2014,
Pubmed
Fugmann,
The RAG proteins and V(D)J recombination: complexes, ends, and transposition.
2000,
Pubmed
Fugmann,
Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complex.
2000,
Pubmed
Fugmann,
An ancient evolutionary origin of the Rag1/2 gene locus.
2006,
Pubmed
,
Echinobase
Fugmann,
The origins of the Rag genes--from transposition to V(D)J recombination.
2010,
Pubmed
Grundy,
Autoinhibition of DNA cleavage mediated by RAG1 and RAG2 is overcome by an epigenetic signal in V(D)J recombination.
2010,
Pubmed
Gwyn,
A zinc site in the C-terminal domain of RAG1 is essential for DNA cleavage activity.
2009,
Pubmed
Hencken,
Functional characterization of an active Rag-like transposase.
2012,
Pubmed
Hiom,
DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations.
1998,
Pubmed
Hirano,
Evolutionary implications of a third lymphocyte lineage in lampreys.
2013,
Pubmed
Hirano,
The evolution of adaptive immunity in vertebrates.
2011,
Pubmed
Huang,
Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination.
2016,
Pubmed
Huang,
Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes.
2014,
Pubmed
Ji,
The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci.
2010,
Pubmed
Jiang,
Cell cycle-dependent accumulation in vivo of transposition-competent complexes between recombination signal ends and full-length RAG proteins.
2004,
Pubmed
Jiang,
Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to the cell cycle.
2005,
Pubmed
Jones,
The roles of the RAG1 and RAG2 "non-core" regions in V(D)J recombination and lymphocyte development.
2009,
Pubmed
Jones,
The taming of a transposon: V(D)J recombination and the immune system.
2004,
Pubmed
Jones,
Autoubiquitylation of the V(D)J recombinase protein RAG1.
2003,
Pubmed
Kapitonov,
RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons.
2005,
Pubmed
,
Echinobase
Kapitonov,
Molecular paleontology of transposable elements in the Drosophila melanogaster genome.
2003,
Pubmed
Kapitonov,
Evolution of the RAG1-RAG2 locus: both proteins came from the same transposon.
2015,
Pubmed
,
Echinobase
Kassmeier,
VprBP binds full-length RAG1 and is required for B-cell development and V(D)J recombination fidelity.
2012,
Pubmed
Kennedy,
Tn10 transposition via a DNA hairpin intermediate.
1998,
Pubmed
Kim,
Crystal structure of the V(D)J recombinase RAG1-RAG2.
2015,
Pubmed
Kim,
Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase.
1999,
Pubmed
Landree,
Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination.
1999,
Pubmed
Lee,
RAG proteins shepherd double-strand breaks to a specific pathway, suppressing error-prone repair, but RAG nicking initiates homologous recombination.
2004,
Pubmed
Lieber,
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway.
2010,
Pubmed
Lin,
Cell cycle regulation of V(D)J recombination-activating protein RAG-2.
1994,
Pubmed
Litman,
The origins of vertebrate adaptive immunity.
2010,
Pubmed
Liu,
A plant homeodomain in RAG-2 that binds Hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement.
2007,
Pubmed
Maman,
RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2.
2016,
Pubmed
Matthews,
RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination.
2007,
Pubmed
McBlane,
Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps.
1995,
Pubmed
McMahan,
A basic motif in the N-terminal region of RAG1 enhances V(D)J recombination activity.
1997,
Pubmed
Montaudouin,
Endogenous TCR recombination in TCR Tg single RAG-deficient mice uncovered by robust in vivo T cell activation and selection.
2010,
Pubmed
Oettinger,
RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination.
1990,
Pubmed
Panchin,
Molluscan mobile elements similar to the vertebrate Recombination-Activating Genes.
2008,
Pubmed
Ramsden,
Conservation of sequence in recombination signal sequence spacers.
1994,
Pubmed
Raval,
Evidence for Ku70/Ku80 association with full-length RAG1.
2008,
Pubmed
Reddy,
Genomic instability due to V(D)J recombination-associated transposition.
2006,
Pubmed
Rodgers,
A zinc-binding domain involved in the dimerization of RAG1.
1996,
Pubmed
Rogozin,
Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase.
2007,
Pubmed
Roman,
Complementation of V(D)J recombination deficiency in RAG-1(-/-) B cells reveals a requirement for novel elements in the N-terminus of RAG-1.
1997,
Pubmed
Rooney,
The role of the non-homologous end-joining pathway in lymphocyte development.
2004,
Pubmed
Ru,
Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures.
2015,
Pubmed
Sakano,
Sequences at the somatic recombination sites of immunoglobulin light-chain genes.
1979,
Pubmed
Schatz,
V(D)J recombination: mechanisms of initiation.
2011,
Pubmed
Schatz,
The V(D)J recombination activating gene, RAG-1.
1989,
Pubmed
Steen,
Roles of the "dispensable" portions of RAG-1 and RAG-2 in V(D)J recombination.
1999,
Pubmed
Swanson,
Full-length RAG-2, and not full-length RAG-1, specifically suppresses RAG-mediated transposition but not hybrid joint formation or disintegration.
2004,
Pubmed
Swanson,
The bounty of RAGs: recombination signal complexes and reaction outcomes.
2004,
Pubmed
Teng,
RAG Represents a Widespread Threat to the Lymphocyte Genome.
2015,
Pubmed
Thompson,
New insights into V(D)J recombination and its role in the evolution of the immune system.
1995,
Pubmed
Tsai,
DNA mismatches and GC-rich motifs target transposition by the RAG1/RAG2 transposase.
2003,
Pubmed
Tsai,
Regulation of RAG1/RAG2-mediated transposition by GTP and the C-terminal region of RAG2.
2003,
Pubmed
Wilson,
The PHD domain of the sea urchin RAG2 homolog, SpRAG2L, recognizes dimethylated lysine 4 in histone H3 tails.
2008,
Pubmed
,
Echinobase
Yin,
Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis.
2009,
Pubmed
Yurchenko,
The RAG1 N-terminal domain is an E3 ubiquitin ligase.
2003,
Pubmed
Zhang,
An amphioxus RAG1-like DNA fragment encodes a functional central domain of vertebrate core RAG1.
2014,
Pubmed
Zhou,
Transposition of hAT elements links transposable elements and V(D)J recombination.
2004,
Pubmed
van Gent,
Similarities between initiation of V(D)J recombination and retroviral integration.
1996,
Pubmed
