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One to rule them all: A highly conserved motif in mariner transposase controls multiple steps of transposition

Bouuaert, Corentin Claeys; Chalmers, Ronald; Tellier, Michael

Authors

Corentin Claeys Bouuaert

RONALD CHALMERS RONALD.CHALMERS@NOTTINGHAM.AC.UK
Professor of Biochemistry and Cell Biology

Michael Tellier



Abstract

The development of transposon-based genome manipulation tools can benefit greatly from understanding transposons’ inherent regulatory mechanisms. The Tc1-mariner transposons, which are being widely used in biotechnological applications, are subject to a self-inhibitory mechanism whereby increasing transposase expression beyond a certain point decreases the rate of transposition. In a recent paper, Liu and Chalmers performed saturating mutagenesis on the highly conserved WVPHEL motif in the mariner-family transposase from the Hsmar1 element. Curiously, they found that the majority of all possible single mutations were hyperactive. Biochemical characterizations of the mutants revealed that the hyperactivity is due to a defect in communication between transposase subunits, which normally regulates transposition by reducing the rate of synapsis. This provides important clues for improving transposon-based tools. However, some WVPHEL mutants also showed features that would be undesirable for most biotechnological applications: they showed uncontrolled DNA cleavage activities and defects in the coordination of cleavage between the two transposon ends. The study illustrates how the knowledge of inhibitory mechanisms can help improve transposon tools but also highlights an important challenge, which is to specifically target a regulatory mechanism without affecting other important functions of the transposase.

Citation

Bouuaert, C. C., Chalmers, R., & Tellier, M. (2014). One to rule them all: A highly conserved motif in mariner transposase controls multiple steps of transposition. Mobile Genetic Elements, 4(2), https://doi.org/10.4161/mge.28807

Journal Article Type Article
Acceptance Date Jul 4, 2014
Online Publication Date Apr 14, 2014
Publication Date 2014-03
Deposit Date Mar 17, 2017
Journal Mobile Genetic Elements
Print ISSN 2159-2543
Publisher Taylor & Francis Open
Peer Reviewed Peer Reviewed
Volume 4
Issue 2
Article Number e28807
DOI https://doi.org/10.4161/mge.28807
Public URL http://www.ncbi.nlm.nih.gov/pubmed/24812590
Publisher URL https://www.tandfonline.com/doi/full/10.4161/mge.28807
Additional Information Peer Review Statement: The publishing and review policy for this title is described in its Aims & Scope.; Aim & Scope: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=kmge20