DNA repair defects sensitize cells to anticodon nuclease yeast killer toxins |
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Authors: | Roland Klassen Sabrina Wemhoff Jens Krause Friedhelm Meinhardt |
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Institution: | 1.Institut für Molekulare Mikrobiologie und Biotechnologie,Westf?lische Wilhelms-Universit?t Münster,Münster,Germany;2.Department of Biochemistry and Molecular Biology,University of Texas Medical Branch,Galveston,USA;3.Chair of Genetics of Prokaryotes, Faculty of Biology,University of Bielefeld,Bielefeld,Germany |
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Abstract: | Killer toxins from Kluyveromyces lactis (zymocin) and Pichia acaciae (PaT) were found to disable translation in target cells by virtue of anticodon nuclease (ACNase) activities on tRNAGlu and tRNAGln, respectively. Surprisingly, however, ACNase exposure does not only impair translation, but also affects genome integrity
and concomitantly DNA damage occurs. Previously, it was shown that homologous recombination protects cells from ACNase toxicity.
Here, we have analyzed whether other DNA repair pathways are functional in conferring ACNase resistance as well. In addition
to HR, base excision repair (BER) and postreplication repair (PRR) promote clear resistance to either, PaT and zymocin. Comparative
toxin sensitivity analysis of BER mutants revealed that its ACNase protective function is due to the endonucleases acting
on apurinic (AP) sites, whereas none of the known DNA glycosylases is involved. Because PaT and zymocin require the presence
of the ELP3/TRM9-dependent wobble uridine modification 5-methoxy-carbonyl-methyl (mcm5) for tRNA cleavage, we analyzed toxin response in DNA repair mutants additionally lacking such tRNA modifications. ACNase
resistance caused by elp3 or trm9 mutations was found to rescue hypersensitivity of DNA repair defects, consistent with DNA damage to occur as a consequence
of tRNA cleavage. The obtained genetic evidence promises to reveal new aspects into the mechanism linking translational fidelity
and genome surveillance. |
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