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An RNA polymerase III subunit determines sites of retrotransposon integration

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Science  01 May 2015:
Vol. 348, Issue 6234, pp. 585-588
DOI: 10.1126/science.1259114

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Keeping jumping genes out of harm's way

The genomes of most eukaryotes, including our own, are jam-packed with parasitic mobile DNA elements. Most are nonfunctional remnants, but a few are still active, capable of jumping about in our DNA, potentially causing serious damage to our genes. Nevertheless, they avoid landing in and disrupting coding regions. For example, in yeast, the retrotransposon Ty1 is targeted away from protein genes to positions upstream of yeast RNA polymerase III genes. Bridier-Nahmias et al. show that Ty1 is targeted to these “safe havens” through an interaction between a Ty1-encoded protein that controls its genome jumping activity and a subunit of the yeast RNA polymerase III complex.

Science, this issue p. 585

Abstract

Mobile genetic elements are ubiquitous. Their integration site influences genome stability and gene expression. The Ty1 retrotransposon of the yeast Saccharomyces cerevisiae integrates upstream of RNA polymerase III (Pol III)–transcribed genes, yet the primary determinant of target specificity has remained elusive. Here we describe an interaction between Ty1 integrase and the AC40 subunit of Pol III and demonstrate that AC40 is the predominant determinant targeting Ty1 integration upstream of Pol III–transcribed genes. Lack of an integrase-AC40 interaction dramatically alters target site choice, leading to a redistribution of Ty1 insertions in the genome, mainly to chromosome ends. The mechanism of target specificity allows Ty1 to proliferate and yet minimizes genetic damage to its host.

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