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Hyperactive mariner transposons are created by mutations that disrupt allosterism and increase the rate of transposon end synapsis

Liu, Danxu; Chalmers, Ronald

Authors

Danxu Liu

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



Abstract

New applications for transposons in vertebrate genetics have spurred efforts to develop hyperactive variants. Typically, a genetic screen is used to identify several hyperactive point mutations, which are then incorporated in a single transposase gene. However, the mechanisms responsible for the increased activity are unknown. Here we show that several point mutations in the mariner transposase increase their activities by disrupting the allostery that normally serves to downregulate transposition by slowing synapsis of the transposon ends. We focused on the conserved WVPHEL amino acid motif, which forms part of the mariner transposase dimer interface. We generated almost all possible single substitutions of the W, V, E and L residues and found that the majority are hyperactive. Biochemical analysis of the mutations revealed that they disrupt signals that pass between opposite sides of the developing transpososome in response to transposon end binding. In addition to their role in allostery, the signals control the initiation of catalysis, thereby preventing non-productive double-strand breaks. Finally, we note that such breaks may explain the puzzling ‘self-inflicted wounds’ at the ends of the Mos1 transposon in Drosophila.

Citation

Liu, D., & Chalmers, R. (2014). Hyperactive mariner transposons are created by mutations that disrupt allosterism and increase the rate of transposon end synapsis. Nucleic Acids Research, 42(4), https://doi.org/10.1093/nar/gkt1218

Journal Article Type Article
Acceptance Date Nov 5, 2013
Online Publication Date Dec 5, 2013
Publication Date Feb 1, 2014
Deposit Date Mar 22, 2017
Publicly Available Date Mar 28, 2024
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 42
Issue 4
DOI https://doi.org/10.1093/nar/gkt1218
Public URL https://nottingham-repository.worktribe.com/output/997095
Publisher URL https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkt1218

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