There are a limited number of transposase types
defined by their chemistry.
The main groups
Two groups whose mechanisms are the best understood
are the DDE and the HUH superfamilies named after the amino acids which
constitute the active sites. The reaction mechanisms involved in
transposition using DDE enzymes have been treated in depth (e.g. (Mizuuchi, 1992, Mizuuchi, 1997, Mizuuchi & Baker, 2002, Hickman &
Dyda, 2015)) as have those of the HUH enzymes (see (Chandler, et al., 2013, He, et al., 2015)).
Other types of transposase include: the DEDD enzymes (Buchner, et al., 2005) whose chemistry presumably resembles that of the
DDE enzymes (since they also
have an RNaseH fold (Ariyoshi, et al., 1994)) but
resemble the RuvC four-way Holliday junction resolvase; Serine transposases which are thought to use
chemistry similar to their Serine-site-specific recombinase cousins; and a
group of novel transposons, casposons, thought to be primitive ancestors of the
CRISPR system (Krupovic, et al., 2014).
Most transposition reactions can be divided into
several defined steps generally comprising: binding of the transposase to the
ends; elaboration of a synaptic complex involving the transposase, perhaps
accessory proteins, and both transposon ends - this step involves either
concomitant or subsequent (depending on the element) recruitment of the target
DNA; cleavage and strand transfer of the transposon ends into the target; and
processing of the strand transfer complex to a final product. The protein-DNA complexes assembled during this process are
Enzymes or reaction components?
important point which has not yet been fully addressed is whether transposases
are true enzymes which can be recycled or whether they are themselves reaction
components which are consumed during the process. The fact that many
transposases show a preference for action on the element from which they are
expressed (in cis) and the coupling between transposase translation and DNA
binding (Duval-Valentin & Chandler, 2011) imposes strong constraints on transposase recycling. Moreover, at least in the
case of bacteriophage Mu, special machinery in place for removing transposase
from the transposition complex following insertion which includes ClpX (Mhammedi-Alaoui, et al., 1994) (Kruklitis, et al.,
1996), (Levchenko, et al., 1995). In addition, the Lon
protease is implicated in proteolysis of the IS903 transposase (Derbyshire, et al., 1990,
Derbyshire & Grindley, 1996).
- Ariyoshi M, Vassylyev DG, Iwasaki H, Nakamura H,
Shinagawa H & Morikawa K (1994) Atomic structure of the RuvC resolvase: a
holliday junction-specific endonuclease from E. coli. Cell 78: 1063-1072.
- Buchner JM, Robertson AE, Poynter DJ, Denniston SS
& Karls AC (2005) Piv Site-Specific Invertase Requires a DEDD Motif Analogous
to the Catalytic Center of the RuvC Holliday Junction Resolvases. 10.1128/JB.187.10.3431-3437.2005. J. Bacteriol. 187: 3431-3437.
- Chandler M, de la Cruz F, Dyda F, Hickman AB, Moncalian
G & Ton-Hoang B (2013) Breaking and joining single-stranded DNA: the HUH
endonuclease superfamily. Nat Rev
Microbiol 11: 525-538.
- Derbyshire KM & Grindley ND (1996) Cis preference
of the IS903 transposase is mediated by a combination of transposase
instability and inefficient translation. Mol
Microbiol 21: 1261-1272.
- Derbyshire KM, Kramer M & Grindley ND (1990) Role
of instability in the cis action of the insertion sequence IS903 transposase. Proc Natl Acad Sci U S A 87: 4048-4052.
- Duval-Valentin G & Chandler M (2011)
Cotranslational control of DNA transposition: a window of opportunity. Mol Cell 44: 989-996.
- He S, Corneloup A, Guynet C, et al. (2015) The IS200/IS605 Family and "Peel and
Paste" Single-strand Transposition Mechanism. Microbiol Spectr 3.
- Hickman AB & Dyda F (2015) Mechanisms of DNA
Transposition. Microbiol Spectr 3: MDNA3-0034-2014.
- Kruklitis R, Welty DJ & Nakai H (1996) ClpX protein
of Escherichia coli activates bacteriophage Mu transposase in the strand
transfer complex for initiation of Mu DNA synthesis. EMBO J. 15: 935-944.
- Krupovic M, Makarova KS, Forterre P, Prangishvili D
& Koonin EV (2014) Casposons: a new superfamily of self-synthesizing DNA
transposons at the origin of prokaryotic CRISPR-Cas immunity. BMC Biol 12: 36.
- Levchenko I, Luo L & Baker TA (1995) Disassembly of
the Mu transposase tetramer by the ClpX chaperone. Genes Dev 9: 2399-2408.
- Mhammedi-Alaoui A, Pato M, Gama MJ & Toussaint A
(1994) A new component of bacteriophage Mu replicative transposition machinery:
the Escherichia coli ClpX protein. Mol.Microbiol. 11: 1109-1116.
- Mizuuchi K (1992) Polynucleotidyl transfer reactions in
transpositional DNA recombination. J Biol
Chem 267: 21273-21276.
- Mizuuchi K (1997) Polynucleotidyl transfer reactions in
site-specific DNA recombination. Genes
Cells 2: 1-12.
K & Baker TA (2002) Chemical mechanisms for mobilizing DNA. Mobile DNA, Vol. II (Craig NL, Craigie
R, Gellert M & Lambowitz A, ed.^eds.), p.^pp. 12-23. ASM press, Washington