Key Points
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The recent DNA sequence determination of the human, mouse and rice genomes has highlighted the abundant and diverse nature of transposons; approximately 40% of the genomes are composed of repetitive elements.
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The mechanisms for how these elements move and cause chromosomal rearrangements are derived from the many elegant genetic, molecular and structural studies carried out on transposons found in model organisms.
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Transposons can be organized into five families based on their encoded transposases, which dictate how they move. Although mechanistic details of transposition have been determined for a relatively small number of elements, the organization of transposons based on their probable catalytic mechanism provides a useful framework for predicting the movement and rearrangements caused by the elements still to be characterized.
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DDE-transposons encode a transposase that has a related amino-acid motif (the DDE motif), which forms the active site of the transposase and is responsible for coordinating the cleavage and joining steps of transposition.
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Tyrosine (Y)-transposons encode transposases that are related to tyrosine recombinases, which normally promote site-specific recombination. These elements transpose using an active-site tyrosine to cleave transposon and target DNA. Importantly, theY-transposases lack the site-specificity of their site-specific cousins and therefore have the ability to insert into many different target sites.
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Serine (S)-transposons, which are newly discovered elements, encode transposases that are related to site-specific serine recombinases. As for Y-transposases, it is thought that the ability of S-transposases to recognize different sequences allows S-transposons to insert into unrelated targets.
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Y2-transposons (or rolling-circle transposons) move by a mechanism that resembles rolling-circle replication as carried out by many bacterial plasmids and phage. The Y2-transposase contains several motifs (including a pair of tyrosine residues) that are conserved among plasmid and phage rolling-circle replication proteins, which are important for DNA binding and catalysis.
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Target-primed (TP)-retrotransposons use a combination of reverse transcriptase and endonuclease activities to reverse transcribe an RNA copy of their genome directly into a target.
Abstract
Transposons are ubiquitous in prokaryotic and eukaryotic organisms and are major determinants of genome structure. Transposition — the movement of discrete segments of DNA without a requirement for homology — occurs by a handful of mechanisms that are used over and over again in different combinations. Understanding these mechanisms provides an important key to unlocking the secrets of genome organization and evolution.
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Acknowledgements
We thank M. Belfort for comments on this work and, in particular, N. Grindley for his enthusiastic discussions on transposon families and mechanisms. This work was supported by the National Institutes of Health.
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DATABASES
Swiss-Prot
FURTHER INFORMATION
Flybase, Drosophila Transposons, Transgene Constructs, and Insertions
Glossary
- TRANSPOSABLE ELEMENT
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A transposable element or a transposon is a defined segment of DNA that has the ability to move, or copy itself, into a second location without a requirement for DNA homology.
- TRANSPOSASE
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An enzyme that is responsible for the catalysis of transposition.
- DDE
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A triad of highly conserved amino acids (aspartate (D), aspartate, glutamate (E)) that is found in one class of transposases, which are required for the coordination of metal ions that are necessary for catalysis.
- REVERSE TRANSCRIPTASE
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A DNA polymerase that can use RNA as a template for the synthesis of a cDNA.
- ENDONUCLEASE
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An enzyme that catalyzes the cleavage of a phosphodiester bond within a DNA molecule.
- TYROSINE RECOMBINASE
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An enzyme that is capable of rearranging DNA using a conserved tyrosine residue to cleave and reseal its substrates by a 3′-phosphotyrosine linkage (also known as integrase).
- SERINE RECOMBINASE
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Recombination protein (also known as resolvase or invertase) that uses an active-site serine nucleophile to perform strand-cleavage and religation steps through a 5′-phosphoserine intermediate.
- CONJUGATIVE TRANSPOSON
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A transposon that encodes functions allowing transfer of the transposon DNA between donor and recipient bacterial cells.
- RETROTRANSPOSON
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A transposon, the movement of which occurs through an RNA intermediate, which is copied into a cDNA molecule.
- LTR
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(Long terminal repeat). A directly repeated sequence at each end of a retrovirus or retrotransposon, which is necessary for reverse transcription, integration and transcription.
- INTEGRASE
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A term used to describe two different protein families that integrate one DNA molecule into another, but by two different mechanisms. 1: a DDE-containing protein of LTR-retrotransposons and retroviruses that catalyses the integration of a cDNA molecule into a target DNA. 2: a member of the tyrosine site-specific recombinases that is responsible for catalysing the integration and excision of DNA, most notably bacteriophage λ.
- DNA HYDROLYSIS
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Cleavage of a DNA backbone by an activated water molecule, resulting in the addition of an OH group to the 3′ or 5′ position of the ribose.
- TRANS-ESTERIFICATION
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The direct exchange of an alcohol moiety of an ester for another alcohol. In this case, the OH group on the 3′ end of the transposon or an amino acid (Y or S) is exchanged for the phospho-ester group on a DNA target.
- TRANSPOSOSOME
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A protein–DNA complex that mediates all the steps of transposition, ensuring the fidelity of the reaction. The complex contains both cis-acting sites (for example, transposon ends), target and transposase protein (and sometimes other host factors).
- NUCLEOPHILIC ATTACK
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A reaction that involves the transfer of electrons from a nucleophile; for example, a hydroxyl group from H2O or a serine or tyrosine residue.
- NON-HOMOLOGOUS END-JOINING
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The joining of DNA ends that share no, or only a few, nucleotides of DNA homology.
- P NUCLEOTIDE
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(Palindromic nucleotide). A small, palindromic DNA sequence that is introduced at the site of hairpin resolution during excision of Tam3-related elements and V(D)J signal sequences.
- TYPE IIS RESTRICTION ENDONUCLEASE
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A DNA endonuclease that recognizes an asymmetric sequence and cleaves both DNA strands at fixed positions outside the recognition site.
- RAG PROTEIN
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Protein product of the recombination-activating genes that are required for V(D)J recombination.
- SYNAPTIC COMPLEX
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A protein–DNA complex, or transpososome, that contains DNA sites in the correct alignment for effective recombination.
- RNASE H
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An enzyme that degrades the RNA strand of an RNA–DNA duplex.
- CONJUGAL RELAXASE
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A protein that is responsible for initiating DNA transfer in bacteria. It contains a conserved tyrosine motif that is required to nick the transferred DNA strand at oriT, which it forms a 5′-phosphotyrosine bond with.
- HELICASE
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An enzyme that promotes ATP-dependent disassociation of the complementary DNA or RNA strands of a duplex molecule.
- DEAD BOX
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An evolutionarily conserved array of amino acids, also known as the Walker B motif, that confers ATP-binding activity.
- LINE
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(Long interspersed nuclear element). A retrotransposon, the mobility of which is dependent on target-primed reverse transcription.
- GROUP II INTRON
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An autocatalytic intron from one of two families that catalyses its own splicing from an RNA transcript and encodes a protein that mediates its mobility as a DNA element. Group II introns are the likely progenitors of spliceosomal introns.
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Curcio, M., Derbyshire, K. The outs and ins of transposition: from Mu to Kangaroo. Nat Rev Mol Cell Biol 4, 865–877 (2003). https://doi.org/10.1038/nrm1241
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DOI: https://doi.org/10.1038/nrm1241
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