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Nat Commun. 2018 Dec 21;9(1):5417. doi: 10.1038/s41467-018-07836-0.

Distinct adaptive mechanisms drive recovery from aneuploidy caused by loss of the Ulp2 SUMO protease.

Author information

1
Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, 06520, USA.
2
Yale Center for Genome Analysis, Yale University, New Haven, CT, 06520, USA.
3
Department of Immunobiology, Yale University, New Haven, CT, 06520, USA.
4
Department of Biology, Molecular Microbiology, University of Konstanz, Universitaetsstrasse 10, 78457, Konstanz, Germany.
5
Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, 06520, USA. mark.hochstrasser@yale.edu.

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.

PMID:
30575729
PMCID:
PMC6303320
DOI:
10.1038/s41467-018-07836-0
[Indexed for MEDLINE]
Free PMC Article

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