Distinct adaptive mechanisms drive recovery from aneuploidy caused by loss of the Ulp2 SUMO protease View Full Text


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Article Info

DATE

2018-12-21

AUTHORS

Hong-Yeoul Ryu, Francesc López-Giráldez, James Knight, Soo Seok Hwang, Christina Renner, Stefan G. Kreft, Mark Hochstrasser

ABSTRACT

In response to acute loss of the Ulp2 SUMO-specific protease, yeast become disomic for chromosome I (ChrI) and ChrXII. Here we report that ChrI disomy, which creates an adaptive advantage in part by increasing the dosage of the Ccr4 deadenylase, was eliminated by extended passaging. Loss of aneuploidy is often accompanied by mutations in essential SUMO-ligating enzymes, which reduced polySUMO-conjugate accumulation. The mRNA levels for almost all ribosomal proteins increase transiently upon initial loss of Ulp2, but elevated Ccr4 levels limit excess ribosome formation. Notably, extended passaging leads to increased levels of many small nucleolar RNAs (snoRNAs) involved in ribosome biogenesis, and higher dosage of three linked ChrXII snoRNA genes suppressed ChrXII disomy in ulp2Δ cells. Our data reveal that aneuploidy allows rapid adaptation to Ulp2 loss, but long-term adaptation restores euploidy. Cellular evolution restores homeostasis through countervailing mutations in SUMO-modification pathways and regulatory shifts in ribosome biogenesis. More... »

PAGES

5417

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-07836-0

    DOI

    http://dx.doi.org/10.1038/s41467-018-07836-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1110718621

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30575729


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