The HUH Enzymes
TE encoding the second
major type of Tpase, called HUH (named for the conserved active site amino acid residues H=Histidine and
U=large hydrophobic residue)(Figs 1.7.1 and 1.10.1), have been identified more
recently. HUH enzymes are widespread single strand nucleases. They include Rep
proteins involved in bacteriophage and plasmid rolling circle replication and
relaxases or Mob proteins involved in conjugative plasmid transfer (Chandler, et
al., 2013). They are limited to two prokaryotic (IS91 and IS200/IS605; (He, et al., 2015)) and one
eukaryotic (helitron; (Thomas & Pritham,
2015)) TE family. As Tpases, they are involved in presumed rolling
circle transposition and also in single-strand transposition (see (Hickman & Dyda, 2015);(He, et al.,
2015)). Not only is the transposition chemistry radically different to
that of DDE group elements, since it involves DNA cleavage using a tyrosine
residue and transient formation of a phospho-tyrosine bond, but the associated
transposons have an entirely different organization and include sub-terminal
secondary structures instead of IRs (see IS families below, (He, et al.,
2015). Note that
these Tpases are not related to the well characterised tyrosine site-specific
recombinases such as phage integrases.
There are two major HUH
Tpase families: Y1 and Y2 enzymes (Fig 1.7.1) (see (Chandler, et al., 2013))
depending on whether there is a single or two catalytic Y residues. One family
includes IS91-family transposases (Zabala, et al.,
1982, Garcillan-Barcia, et al., 2002),
the other includes IS200/IS605 transposases (Lam & Roth, 1983, Kersulyte, et al., 2002). Although these enzymes use the same Y-mediated cleavage mechanism, IS200/IS605 family Y1 transposases and IS91 transposases appear to carry out the transposition process in
quite different ways. Neither carries terminal IRs nor do they generate DRs on
insertion. Members of these families transpose using an entirely different
mechanism to IS with DDE transposases (del Pilar
Garcillan-Barcia, et al., 2001,
Ton-Hoang, et al., 2005). The members
of the IS91 insertion sequence family (Mendiola & de la Cruz, 1992), are
related to newly defined group, the ISCR (Toleman, et al., 2006) (see IS91-related ISCRs) and with eukaryotic helitrons (Fig 1.7.1) (Kapitonov
& Jurka, 2007). These IS carry sub-terminal sequences which are able
to form hairpin secondary structures (Fig 1.3.2). This is particularly marked in
the IS200/IS605 family elements and, at least in the case of this family, it is
these structures which are recognised by the transposase (He, et al.,
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.
Pilar Garcillan-Barcia M, Bernales I, Mendiola MV & de la Cruz F (2001)
Single-stranded DNA intermediates in IS91 rolling-circle transposition. Mol Microbiol 39: 494-501.
- Garcillan-Barcia MP, Bernales
I, Mendiola MV & De la Cruz F (2002) IS91 rolling circle transposition. Mobile DNA, Vol. II (Craig NL, Craigie R, Gellert M & Lambowitz A, ed.^eds.), p.^pp.
891-904. ASM press, Washington DC.
- He S,
Corneloup A, Guynet C, et al. (2015)
The IS200/IS605 Family and "Peel and Paste" Single-strand
Transposition Mechanism. Microbiol Spectr 3.
AB & Dyda F (2015) Mechanisms of DNA Transposition. Microbiol Spectr 3:
VV & Jurka J (2007) Helitrons on a roll: eukaryotic rolling-circle
transposons. Trends Genet 23: 521-529.
D, Velapatino B, Dailide G, et al. (2002) Transposable element ISHp608 of Helicobacter pylori: nonrandom
geographic distribution, functional organization, and insertion specificity. J.Bacteriol. 184: 992-1002.
- Lam S
& Roth JR (1983) IS200: a Salmonella-specific insertion sequence. Cell 34: 951-960.
MV & de la Cruz F (1992) IS91 transposase is related to the
rolling-circle-type replication proteins of the pUB110 family of plasmids. Nucleic Acids Res. 20: 3521-3521.
J & Pritham EJ (2015) Helitrons, the Eukaryotic Rolling-circle Transposable
Elements. Microbiol Spectr 3.
MA, Bennett PM & Walsh TR (2006) ISCR Elements: Novel Gene-Capturing
Systems of the 21st Century? Microbiol
Mol Biol Rev 70: 296-316.
B, Guynet C, Ronning DR, Cointin-Marty B, Dyda F & Chandler M (2005)
Transposition of ISHp608, member of an unusual family of bacterial insertion
sequences. Embo J 24: 3325-3338.
- Zabala JC, de la Cruz F & Ortiz
JM (1982) Several copies of the same insertion sequence are present in
alpha-hemolytic plasmids belonging to four different incompatibility groups. J Bacteriol 151: 472-476.