General features and properties of insertion sequence elements

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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., 2015).

    References :
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