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Chapter 1 : A Moveable Feast: An Introduction to Mobile DNA

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Abstract:

DNA has two critical functions: to provide the cell with the information necessary for macromolecular synthesis and to transmit that information to progeny cells. Genome sequence stability is important for both these functions. Indeed, cells devote significant resources to various DNA repair processes that maintain genome structure and repair alterations that can arise from DNA synthesis errors and assaults from both endogenous and exogenous sources. DNA sequence variation, however, provides the substrate for adaptation, selection, and evolution.

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014

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Mobile Genetic Elements
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Gene Expression and Regulation
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Figure 1

A targeted DNA double strand break can lead to gene insertion. Introduction of a site-specific double strand break by a homing endonuclease (HEN) in a homologous DNA duplex lacking the HEN gene targets homology-dependent DNA synthesis (green) that introduces a copy of the HEN gene to the broken DNA. doi:10.1128/microbiolspec.MDNA3-0062-2014.f1

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 2

A targeted DNA double strand break causes mating type switching in . Information that specifies either mating type or mating type α is expressed at and is also present at silent storage sites and . Introduction of a DNA double strand break in by the endonuclease HO targets homology-dependent DNA synthesis at using either the silent and storage sites as templates. DNA breaks in cells use silent α as the donor, thus switching to α, resulting in a switch in mating type from to α. Conversely, cleavage results in a switch to α. doi:10.1128/microbiolspec.MDNA3-0062-2014.f2

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 3

Gene replacement underlies antigenic variation in . A pilin surface antigen is expressed from the site and multiple variant pilin genes are stored in silent sites. Homology-dependent repair using template information from a gene changes the information in , varying the surface antigen. doi:10.1128/microbiolspec.MDNA3-0062-2014.f3

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 4

Targeted DNA double strand breaks by RAG mediate immunoglobulin gene assembly during V(D)J recombination. Diverse immunoglobulins that recognize many different antigens result from combinatorial assembly of different V, D, and J coding segments. Site-specific cleavage by RAG, at RSS12 and RSS23 sites that bound the multiple V, D and J segments, results in excision of intervening DNA between the gene segments to be joined and formation of a coding joint by NHEJ. The intervening DNA circularizes, forming a signal joint and is lost from the cell. doi:10.1128/microbiolspec.MDNA3-0062-2014.f4

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 5

Targeted DNA double strand breaks at switch sites join V(D)J coding segments to different antibody class segments. DNA double strand breaks (DSB) are targeted by transcription-induced activation-induced cytidine deaminase (AID) modification of switch sites downstream of an assembled V(D)J coding region and upstream of different antibody class coding regions. The intervening DNA is excised and combinatorial joining of the V(D)J and antibody class segments by NHEJ results in different classes of antibodies. doi:10.1128/microbiolspec.MDNA3-0062-2014.f5

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 6

Different families of DDE transposases mediate the transposition of different elements. Different superfamilies of DDE transposases use different combinations of DNA breakage, replication, and joining reactions to move different DNA transposons (see Chapter 25 for details). Some elements move by excision and integration (cut and paste), whereas the movement of other elements involves copying of the element by DNA replication (nick-copy out-paste and nick-paste-copy). Transposases from different families can use related mechanisms. . 2009. Molecular architecture of the paired-end complex: the structural basis of DNA transposition in a eukaryote. :1096–1108; . 2007. In vitro transposition of , a bacterial insertion sequence belonging to the family. :1432–1443; . 2015. Transposition of a Rice Mutator-Like Element in the Yeast . :132–148; . 2010. Characterization of the transposase encoded by , the prototype of a major family of bacterial insertion sequence elements. :4153–4163. doi:10.1128/microbiolspec.MDNA3-0062-2014.f6

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 7

Some transposons encode DDE Transposases and ATP-utilizing target choice regulators. Bacteriophage uses cut and paste transposition to insert into the bacterial genome and replicative transposition to replicate its DNA during lytic growth. MuA is a DDE transposase that breaks and joins DNA and the ATP-dependent regulator MuB controls target DNA selection. Related transposons also encode a transposase, an ATP-dependent target regulator and, in some cases, an additional target type specification protein. . 1999. family transposons are site hunters sensing plasmidal sites occupied by cognate resolvases. :1059–1068; . 1990. , a novel transposable element from . :961–975. doi:10.1128/microbiolspec.MDNA3-0062-2014.f7

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 8

Mechanism of DNA cut and paste transposition by a DDE transposase. The transposase makes DNA double strand breaks at the transposon ends that excise the element from the donor site, exposing the 3′-OH transposon ends. These 3′-OH ends then attack the two target DNA strands at staggered positions by direct transesterification reactions that covalently link the 3′ transposon ends to the target DNA. The staggered end joining positions result in single strand gaps at the 5′ transposon ends that are repaired by host DNA synthesis (green) to generate flanking target site duplications. doi:10.1128/microbiolspec.MDNA3-0062-2014.f8

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 9

Mechanism of transposition of the nick-copy out and paste transposon by a DDE transposase. Transposition begins by transposase nicking at one transposon end. The resulting 3′-OH then attacks its own 5′ end, circularizing the transposon. DNA replication (green) initiated at a flanking target 3′-OH copies both transposon strands, releasing a circularized transposon and repairing the donor site. Transposase then cleaves the transposon ends in the transposon circle, releasing 3′-OH ends that attack the target DNA. doi:10.1128/microbiolspec.MDNA3-0062-2014.f9

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 10

Mechanism of replicative transposition of by a DDE transposase. Transposition begins by transposase nicking to expose both 3′-OH transposon ends that attack and link to the target DNA while the 5′ transposon ends remain linked to the donor plasmid. Replication (green) initiated at the flanking target 3′-OHs copies both strands of the transposon, generating a cointegrate in which two transposon copies link the donor and target plasmids. DNA breakage, strand exchange and rejoining at the directly oriented sites by the Ser recombinase resolvase that is also encoded by the transposon separates the donor and target plasmids, each containing a transposon copy. doi:10.1128/microbiolspec.MDNA3-0062-2014.f10

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 11

Assembly of an active tetramer of the MuA DDE transposase. The ends of contain multiple bindings sites for the MuA transposase. MuA interaction with the ends results in formation of a MuA tetramer that synapses the two ends and activates DNA breakage and joining by the two transposase protomers bound to the outermost and sites. Internal MuA binding sites in an enhancer (not shown) facilitate tetramer assembly. Usually recruited by MuB (not shown here), a sharply bent target DNA binds to the and promoters, which is attacked by the MuA 3′-OH ends exposed by MuA nicking. doi:10.1128/microbiolspec.MDNA3-0062-2014.f11

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 12

Mechanism of transposition of -like transposable element by a tyrosine (Tyr)-histidine-hydrophobic-histidine (HUH) transposase acting on a single strand DNA substrate. A Tyr-HUH transposase breaks DNA by the attack of the hydroxyl of a higher conserved tyrosine, resulting in a free 3′-OH and a 5′-P-Tyr link. DNA rejoining occurs by attack of the 3′-OH on the 5′-P-Tyr link. Guided by base-pairing interactions between the guide and cleavage sequences at both transposon ends, one protomer of a transposase dimer acts at the upstream transposon end, generating “Donor flank-3′-OH” and “5′-P-Tyr-Transposon end.” The other protomer acts at the downstream transposon end, generating “Transposon end-3′-OH” and “5′-P-Tyr-Donor flank.” The 3′-OHs from one protomer then attack the 5′ phosphotyrosine links on the other protomer. This excises the element as a single strand circle and rejoins the single strand donor site. A transposase dimer then integrates the transposon integration into a single strand DNA target site, guided by the guide and cleavage sequences, by another set of cleavage, strand exchange and rejoining reactions. doi:10.1128/microbiolspec.MDNA3-0062-2014.f12

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 13

Mechanism of transposition of a by a a tyrosine (Tyr)-histidine-hydrophobic-histidine (HUH)/helicase transposase. The Tyr-HUH transposase acts at the upstream end of the transposon, releasing a 3′-OH donor end and a 5′-P-Tyr end. The broken transposon strand is displaced from the donor DNA by rolling circle replication (green) likely assisted by the helicase and it is covalently linked to the target DNA by attack of a target 3′-OH on the 5′-P-Tyr transposon end. DNA synthesis (green) copies the single transposon strand in the target to generate intact duplex DNA. doi:10.1128/microbiolspec.MDNA3-0062-2014.f13

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 14

Mechanism of DNA breakage, strand exchange and joining during conservative site-specific recombination by the Tyrosine recombinase Cre. Cre is a Tyr recombinase that acts at recombination sites consisting of two inverted Cre binding sites flanking a conserved central crossover region. Strand breakage, strand exchange and rejoining by Cre occur at the edges of the crossover region. Cre dimers bind to each site and pair to form the active Cre tetramer that pairs the sites in antiparallel alignment. Recombination begins by cleavage of the two sites on strands of the same polarity, making 3′-P-Tyr and 5′-OH ends. Strand exchange and rejoining occurs by the attack of each 5′-OH on the 3′-P-Tyr of the other strand. The second round of strand exchange occurs by Cre cleavage of the other pair of strands, making 3′-P-Tyr and 5′-OH ends. Strand exchange and rejoining occurs by attack of each 5′-OH on the 3′-P-Tyr of the partner site. Note that because of staggered positions of strand exchange, the recombinant duplexes are heteroduplex in the crossover region, which is bounded by the sites of strand exchange. doi:10.1128/microbiolspec.MDNA3-0062-2014.f14

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 15

The relative orientation of the substrate recombination sites determines the structure of the recombination products. Sites for CSSR consist of two recombinase binding sites flanking a short crossover region of sequence homology sequence, which lacks repeats and is thus asymmetric. Although the local DNA strand breakage and joining reactions are the same in all cases, the overall structure of the recombination products is determined by the relative orientations of the substrate sites. doi:10.1128/microbiolspec.MDNA3-0062-2014.f15

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 16

The sites of Tyrosine recombinase Cre align in antiparallel orientation in the active tetramer. Dimers of Cre bind to each parental site and pair to form the active tetramer in which the sites are aligned in antiparallel fashion. Thus, once cleavage has occurred, strand exchange can occur by local melting and swapping of short, closely juxtaposed DNA segments. Structure graciously provided by Greg Van Duyne. doi:10.1128/microbiolspec.MDNA3-0062-2014.f16

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 17

The integration/ excision cycle of bacteriophage is elaborately regulated. () sites contain two Int core binding sites, COC′ and BOB′, in inverted orientation flanking a 7 bp crossover region of homology, “O,” where strand exchange occurs. COC′ is flanked by and ′ arms containing multiple protein binding sites: P1, P2, P′1, P′2, and P′3 sites = Int arm sites, which have a different recognition sequence than Int core C and B sites. Schematics of the excisive intasome paired substrate DNAs containing and DNAs and the product and DNAs following DNA breakage, strand exchange and rejoining at the “O” regions between the core Int binding sites are shown. H, IHF binding sites; X, Xis binding; F, FIS binding. doi:10.1128/microbiolspec.MDNA3-0062-2014.f17

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 18

Inversion of a promoter-containing DNA segment by the Ser recombinase Hin within an invertasome controls gene expression. Inversion of a DNA segment containing a promoter changes which surface antigen gene is expressed. recombination sites bound the invertible segment in inverted orientation. Hin dimers bind to each site and FIS binds to the enhancer segment. The Hin dimers interact with FIS on the Enhancer platform and with each other to form the active Hin tetramer. Cleavage of both sites occurs in the central region of homology and strands are exchanged by rotation of the upper dimer of Hin, followed by DNA rejoining. Drawing and structures adapted from material from Reid Johnson. doi:10.1128/microbiolspec.MDNA3-0062-2014.f18

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 19

A large Ser integrase can mediate highly regulated cycles of bacteriophage integration and excision. The integration and excision cycle of phage is mediated by a large Serine integrase. Integration between and , which generates the hybrid sites and requires integrase. Excision between and which generates and , requires integrase + recombination directionality factor (RDF). Integrase binds specifically to and using its and domains that recognize and DNA sequences, which are present on all sites. Note the difference in and spacing in vs such that integrase binds to each in a slightly different conformation. CC domains interact with each other. A dimer of Integrase can bind to both and . Pairing between the Int dimers forms the active tetramer, which synapses and . However, an dimer cannot pair with another nor can pair with because of their different Int configurations. Once synapsis occurs, the integrase cleaves the crossover region of homology; the broken DNA ends exchange by rotation of one pair of Integrase subunits, followed by rejoining to generate the hybrid and sites. Note that the CC domains of the dimer integrase bound to and to interact intramolecularly and are thus unavailable for interdimer pairing. RDF is proposed to interact with integrase to change its conformation when bound to and , such that CC domains can interact intermolecularly and pair the dimers on and to form the active tetramer. Excision occurs between and by cleavage of and and subunit rotation, followed by rejoining to generate and . doi:10.1128/microbiolspec.MDNA3-0062-2014.f19

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 20

A Tyr integrase mediates integration of the ICE in the absence of crossover homology between the recombination sites. A hallmark of CSSR crossover regions, which are flanked by inverted recombinase binding sites that promote breakage, exchange and joining at the outer edges of the crossover region, is that the crossover regions are identical. Some Ser and Tyr recombinases can, however, promote recombination between nonhomologous crossover regions. The crossover regions of and of are nonhomologous such that when strand exchange occurs, the heteroduplex regions contain base pair mismatches as shown in this extreme example. Replication of the recombination product yields two daughter chromosomes with different sequences in and . Recombinases that do not require absolute homology can be considered transposases. doi:10.1128/microbiolspec.MDNA3-0062-2014.f20

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 21

A Tyr integrase mediates capture and expression of multiple different gene cassettes. Integrons are gene-expression platforms containing an attachment site () and cognate integrase that are found on other mobile DNAs such as transposons and in bacterial chromosomes. The integron can capture, integrate, and express gene cassettes that contain related but often not identical sites, , by site-specific recombination. Once integration occurs, the P promoter drives expression of the promoter-less cassettes. Some chromosomal integrons contain hundreds of gene cassettes. doi:10.1128/microbiolspec.MDNA3-0062-2014.f21

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 22

Structures of some well-studied retroviruses and retroviral-like retrotransposons. Retroviruses and the closely related retroviral-like retrotransposons contain related central protein-coding regions flanked by direct long terminal repeats. The central regions of both retroviruses and retroviral-like transposons encode Gag, which includes several nucleic acid domains, a protease that cleaves polyprotein precursors, and Pol, which encodes reverse transcriptase, RNase-H and integrase. Retroviruses also encode Env, a membrane protein that facilitates viral particle exit from host cells and entry into new host cells. In different families of retroviruses, different combinations of protein domains are expressed as fusion polyproteins. Some retroviruses also encode other genes, for example, the avian transforming viruses, ASV and RSV, encode the oncogene Src. Reverse transcriptase and RNase-H convert the two viral RNA copies in the viral particle into the DNA form of the virus, which terminates in direct long terminal repeats. Integrase, which is a DDE transposase, integrates the viral DNA into the host genome. In retroviral-like elements of the yeast and family, the order of Gag, Pro and RT, RN and in Pol are the same order as in retroviruses, whereas in the yeast and family, Integrase proceeds RT-RNase H. doi:10.1128/microbiolspec.MDNA3-0062-2014.f22

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 23

A large fraction of the human genome is comprised of transposable elements. The structures of examples of the major classes of transposable elements found in the human genome are shown. Their total copy numbers and the number of estimated active elements are also shown. The active elements, LINE element and the SINES and SVA, whose movement depends on proteins, contribute to human genetic variation. Although processed pseudogenes do not retrotranspose, formation of new pseudogenes has occurred in humans. Note the amount of human genome derived from mobile elements, in some cases significantly (DNA elements=3.4%), or in other cases very dramatically (L1=17.6% and Alu =11%), exceeds the fraction of the human genome that encodes ORFs, about 1.5%. doi:10.1128/microbiolspec.MDNA3-0062-2014.f23

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 24

The mechanism of integration of the DNA forms of retroviruses and retroviral-like retrotransposons. The first step in retroviral replication and integration is transcription of the provirus by host RNA polymerase. Two RNA copies are packaged into each virus particle along with the proteins Reverse transcriptase-RNaseH and IN. Reverse transcriptase uses the two viral RNA copies to synthesize a cDNA (green) extending from the 5′ end of one LTR to the 3′ of the other with exposed 3-OHs. The retroviral integrase, a DDE transposase, inserts the cDNA into the target DNA by direct nucleophillic attack of the 3′-OH cDNA ends at staggered positions on the target. The 5′ gaps are repaired (green) by host functions to give target site duplications. doi:10.1128/microbiolspec.MDNA3-0062-2014.f24

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 25

Retroviral-like retrotransposons in yeast are highly target site-selective. Next gene sequencing has been used to map hundreds of thousands of retroelement insertions in yeast. In , and insert at tRNA genes (and other genes). is highly site-specific, inserting within a nucleotide or two of the transcript start site and is positioned by interaction with tRNA transcription factors. inserts preferentially on nucleosomal DNA within about 1 kb upstream of transcription start sites. inserts preferentially into heterchromatic regions, including telomers. In . , inserts preferentially within about 1 kb upstream upstream of ORF promoters. The regions upstream of some genes are far more attractive to than others. doi:10.1128/microbiolspec.MDNA3-0062-2014.f25

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 26

The non-LTR element R2 inserts site-specifically into rDNA by target-primed reverse transcription. R2 inserts into a specific site in the rDNA genes, which is determined by the target-site selectivity of its own endonuclease. Retrotransposition begins with the formation of a RNP containing R2 RNA and two R2 proteins. The R2 subunit bound to the 3′ end of the RNA nicks the target DNA at a specific sequence. The resulting target 3′-OH is used as a primer for reverse transcription (green) by the element-encoded RT that uses R2 RNA as a template. Reverse transcription extends to the end of the RNA template, followed by cleavage of the top strand by the other subunit. DNA synthesis (green) of the other R2 DNA strand completes insertion of the element. doi:10.1128/microbiolspec.MDNA3-0062-2014.f26

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 27

Long interspersed elements (LINE) elements insert by target-primed reverse transcription into target sites cleaved by ORF2 endonuclease. Transcription of the element initiates retrotransposition. Following synthesis of ORF1 and ORF2 proteins, which associate preferentially with RNA, the RNP enters the nucleus where the ORF2 APE endonuclease makes a nick in the AT-rich target site. Nicking releases a T-rich strand that pairs with the polyA tail of the RNA and the 3′-OH of the target DNA is used as the primer for reverse transcription (green) of the template RNA. Following multiple other processing steps, a new copy of occupies the target DNA. doi:10.1128/microbiolspec.MDNA3-0062-2014.f27

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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Figure 28

Mechanism of group II intron mobility. Transposition begins with transcription of the gene containing the intron, followed by synthesis of the multifunctional intron-encoded protein (IEP) protein that assists in RNA splicing and reverse splicing into the target DNA and has reverse transcriptase and endonuclease activity. After RNA splicing, the excised lariat RNA remains bound to IEP and then reverse splices into an allele of the gene that lacks the intron. This is highly site-specific, being mediated by base pairing between the intronic sequences and exonic sequences in the target DNA. A 3′-OH on the target DNA provides the primer for reverse transcription (green) of the intron, which generates a target gene containing the intron. doi:10.1128/microbiolspec.MDNA3-0062-2014.f28

Citation: Craig N. 2015. A Moveable Feast: An Introduction to Mobile DNA, p 3-39. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0062-2014
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References

/content/book/10.1128/9781555819217.chap1
1. Stoddard B . 2014. Homing endonucleases from mobile group I introns: discovery to genome engineering. Mobile DNA 5 : 7. [PubMed] [CrossRef]
2. Chaumeil J,, Skok J . 2013. A new take on v(d)j recombination: transcription driven nuclear and chromatin reorganization in RAG-mediated cleavage. Front Immunol 4 : 423. [PubMed] [CrossRef]
3. Kim M,, Lapkouski M,, Yang W,, Gellert M . 2015. Crystal structure of the V(D)J recombinase RAG1-RAG2. Nature 518 : 507511.[PubMed] [CrossRef]
4. Jones J,, Gellert M . 2004. The taming of a transposon: V(D)J recombination and the immune system. Immunol Rev 200 : 233248.[PubMed] [CrossRef]
5. Zhou L,, Mitra R,, Atkinson P,, Hickman A,, Dyda F,, Craig NL . 2004. Transposition of hAT elements links transposable elements and V(D)J recombination. Nature 432 : 9951001.[PubMed] [CrossRef]
6. Hickman AB,, Ewis H,, Li X,, Knapp J,, Laver T,, Doss A-L,, Atkinson P,, Craig NL,, Dyda F . 2014. A hAT DNA transposase with an unusual subunit organization to bind long asymmetric ends. Cell 158 : 353367.[PubMed] [CrossRef]
7. Hencken C,, Li X,, Craig NL . 2012. Functional characterization a transposon with a RAG connection. Nat Struct Mol Biol 19 : 834836.[PubMed] [CrossRef]
8. Kapitonov V,, Jurka J . 2005. RAG1 core and V(D)J recombination signal sequnces were derived from Transib transposons. PLoS Biol 3 : e181. [PubMed] [CrossRef]
9. Bracht J,, Fang W,, Goldman A,, Dolzhenko E,, Stein E,, Landweber L . 2013. Genomes on the edge: programmed genome instability in ciliates. Cell 152 : 406416.[PubMed] [CrossRef]
10. Streit A . 2012. Silencing by throwing away: a role for chromatin diminution. Dev Cell 23 : 918919.[PubMed] [CrossRef]
11. Madireddi M,, Coyne R,, Smothers J,, Mickey K,, Yao M,, Allis C . 1996. Pdd1p, a novel chromodomain-containing protein, links heterochromatin assembly and DNA elimination in Tetrahymena. Cell 87 : 7584.[PubMed] [CrossRef]
12. Thomas J,, Phillips C,, Baker R,, Pritham E . 2014. Rolling-circle transposons catalyze genomic innovation in a mammalian lineage. Genome Biol Evol 6 : 25952610.[PubMed] [CrossRef]
13. Ferguson A,, Jiang N . 2011. Pack-MULEs: recycling and reshaping genes through GC-biased acquisition. Mob Genet Elements 1 : 135138.[PubMed] [CrossRef]
14. Feng X,, Colloms S . 2007. In vitro transposition of ISY100, a bacterial insertion sequence belonging to the Tc1/mariner family. Mol Microbiol 65 : 14321443.[PubMed] [CrossRef]
15. Krupovic M,, Makarova K,, Forterre P,, Prangishvili D,, Koonin E . 2014. Casposons: a new superfamily of self-synthesizing DNA transposons at the origin of prokaryotic CRISPR-Cas immunity. BMC Biol 12 : 36. [PubMed] [CrossRef]
16. van der Oost J,, Westra E,, Jackson R,, Wiedenheft B . 2014. Unravelling the structural and mechanistic basis of CRISPR-Cas systems. Nat Rev Microbiol 12 : 479492.[PubMed] [CrossRef]
17. Nunez J,, Lee A,, Engelman A,, Doudna J . 2015. Integrase-mediated spacer acquisition during CRISPR-Cas adaptive immunity. Nature 159 : 193198.[PubMed] [CrossRef]
18. Nunez JK,, Kranzusch P,, Noeske J,, Wright A,, Davies CW,, Doudna J . 2014. Cas1-Cas2 complex formation mediates spacer acquisition during CRISPR-Cas adaptive immunity. Nat Struct Mol Biol 21 : 528534.[PubMed] [CrossRef]
19. Krupovic M,, Koonin EV . 2015. Polintons: a hotbed of eukaryotic virus, transposon and plasmid evolution. Nat Rev Microbiol 13 : 105115.[PubMed] [CrossRef]
20. Yuan Y,, Wessler S . 2011. The catalytic domain of all eukaryotic cut-and-paste transposase superfamilies. Proc Natl Acad Sci U S A 108 : 78847889.[PubMed] [CrossRef]
21. Syvanen M,, Hopkins JD,, Clements M . 1982. A new class of mutants in DNA polymerase I that affects gene transposition. J Mol Biol 158 : 203212.[PubMed] [CrossRef]
22. Han M,, Xu H,, Zhang H,, Feschotte C,, Zhang Z . 2014. Spy: a new group of eukaryotic DNA transposons without target site duplications. Genome Biol Evol 6 : 17481757.[PubMed] [CrossRef]
23. Harshey R . 2012. The Mu story: how a maverick phage moved the field forward. Mobile DNA 3 : 21. [PubMed] [CrossRef]
24. Montano S,, Pigli Y,, Rice P . 2012. The mu transpososome structure sheds light on DDE recombinase evolution. Nature 491 : 413417.[PubMed] [CrossRef]
25. Garcillan-Barcia M,, Bernales I,, Mendiola M,, de la Cruz F, . 2002. IS91 Rolling-Circle Transposition, p 891904. In Craig NL,, Craigie R,, Gellert M,, Lambowitz A (ed), Mobile DNA II. ASM Press, Washington DC.
26. Mitra R,, Li X,, Kapusta A,, Mayhew D,, Mitra R,, Feschotte C,, Craig NL . 2013. Functional characterization of piggyBat from the bat Myotis lucifugus unveils the first active mammalian DNA transposon. Proc Natl Acad Sci U S A 110 : 234239.[PubMed] [CrossRef]
27. Nunes-Duby S,, Azaro M,, Landy A . 1995. Swapping DNA strands and sensing homology without branch migration in lambda site-specific recombination. Curr Biol 5 : 139148.[PubMed] [CrossRef]
28. Birling MC,, Gofflot F,, Warot X . 2009. Site-specific recombinases for manipulation of the mouse genome. Methods Mol Biol 561 : 245263.[PubMed] [CrossRef]
29. Rutherford K,, Van Duyne G . 2014. The ins and outs of serine integrase site-specific recombination. Curr Opin Struct Biol 24 : 125131.[PubMed] [CrossRef]
30. Rutherford K,, Yuan P,, Perry K,, Sharp R,, Van Duyne G . 2013. Attachment site recognition and regulation of directionality by the serine integrases. Nucleic Acids Res 41 : 83418356.[PubMed] [CrossRef]
31. Roberts A,, Mullany P . 2011. Tn916-like genetic elements: a diverse group of modular mobile elements conferring antibiotic resistance. FEMS Microbiol Rev 35 : 856871.[PubMed] [CrossRef]
32. Das B,, Martinez E,, Midonet C,, Barre F . 2013. Integrative mobile elements exploiting Xer recombination. Trends Microbiol 21 : 2330.[PubMed] [CrossRef]
33. Val M,, Bouvier M,, Campos J,, Sherratt D,, Cornet F,, Mazel D,, Barre F . 2005. The single-stranded genome of phage CTX is the form used for integration into the genome of Vibrio cholerae . Mol Cell 19 : 559566.[PubMed] [CrossRef]
34. Goodwin T,, Butler M,, Poulter R . 2003. Cryptons: a group of tyrosine-recombinase-encoding DNA transposons from pathogenic fungi. Microbiology 149 : 30993109.[PubMed] [CrossRef]
35. Kojima K,, Jurka J . 2011. Crypton transposons: identification of new diverse families and ancient domestication events. Mobile DNA 2 : 12. [PubMed] [CrossRef]
36. Doak T,, Witherspoon D,, Jahn C,, Herrick G . 2003. Selection on the genes of Euplotes crassus Tec1 and Tec2 transposons: evolutionary appearance of a programmed frameshift in a Tec2 gene encoding a tyrosine family site-specific recombinase. Eukaryot Cell 2 : 95102.[PubMed] [CrossRef]
37. Jacobs M,, Sanchez-Blanco A,, Katz L,, Klobutcher L . 2003. Tec3, a new developmentally eliminated DNA element in Euplotes crassus. Eukaryot Cell 2 : 103114.[PubMed] [CrossRef]
38. Kazazian H Jr . 2014. Processed pseudogene insertions in somatic cells. Mobile DNA 5 : 20. [PubMed] [CrossRef]
39. Richardson S,, Salvador-Palomeque C,, Faulkner G . 2014. Diversity through duplication: whole-genome sequencing reveals novel gene retrocopies in the human population. Bioessays 36 : 475481.[PubMed] [CrossRef]
40. Coros C,, Piazza C,, Chalamcharla V,, Belfort M . 2008. A mutant screen reveals RNase E as a silencer of group II intron retromobility in Escherichia coli . RNA 14 : 26342644.[PubMed] [CrossRef]
41. Coros C,, Piazza C,, Chalamcharla V,, Smith D,, Belfort M . 2009. Global regulators orchestrate group II intron retromobility. Mol Cell 34 : 250256.[PubMed] [CrossRef]
42. Evgen’ev MB,, Zelentsova H,, Shostak N,, Kozitsina M,, Barskyi V,, Lankenau DH,, Corces VG . 1997. Penelope, a new family of transposable elements and its possible role in hybrid dysgenesis in Drosophila virilis. Proc Natl Acad Sci U S A 94 : 196201.[PubMed] [CrossRef]
43. Pyatkov K,, Arkhipova I,, Malkova N,, Finnegan D,, Evgen’ev M . 2004. Reverse transcriptase and endonuclease activities encoded by Penelope-like retroelements. Proc Natl Acad Sci U S A 101 : 1471914724.[PubMed] [CrossRef]
44. Cervera A,, De la Pena M . 2014. Eukaryotic penelope-like retroelements encode hammerhead ribozyme motifs. Mol Biol Evol 31 : 29412947.[PubMed] [CrossRef]
45. Gladyshev E,, Arkhipova I . 2011. A widespread class of reverse transcriptase-related cellular genes. Proc Natl Acad Sci U S A 108 : 2031120316.[PubMed] [CrossRef]
46. Curcio M,, Belfort M . 1996. Retrohoming: cDNA-mediated mobility of group II introns requires a catalytic RNA. Cell 84 : 912.[PubMed] [CrossRef]
47. Lampson B,, Inouye M,, Inouye S . 2005. Retrons, msDNA, and the bacterial genome. Cytogenet Genome Res 110 : 491499.[PubMed] [CrossRef]
48. Curcio MJ,, Belfort M . 2007. The beginning of the end: links between ancient retroelements and modern telomerases. Proc Natl Acad U S A 104 : 91079108.[PubMed] [CrossRef]

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