Adaptive aneuploidy counters a dysregulated SUMO system

Ryu, Hong‐Yeoul; Hochstrasser, Mark

doi:10.1080/15384101.2016.1256154

Cited by 4 publications

(2 citation statements)

References 7 publications

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“…Although these aneuploidy-mediated compensatory mechanisms help to overcome the acute stress caused by a dysregulated SUMO system, aneuploidy is deleterious, and aneuploid ulp2Δ cultures grow poorly and are highly sensitive to many stresses 50 , 83 . However, in vitro evolution over 250–500 generations restores euploidy 8 .…”

Section: The Ulp2 Sumo Protease and Adaptations To Its Lossmentioning

confidence: 99%

SUMO and cellular adaptive mechanisms

2020

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The ubiquitin family member SUMO is a covalent regulator of proteins that functions in response to various stresses, and defects in SUMO-protein conjugation or deconjugation have been implicated in multiple diseases. The loss of the Ulp2 SUMO protease, which reverses SUMO-protein modifications, in the model eukaryote Saccharomyces cerevisiae is severely detrimental to cell fitness and has emerged as a useful model for studying how cells adapt to SUMO system dysfunction. Both short-term and long-term adaptive mechanisms are triggered depending on the length of time cells spend without this SUMO chain-cleaving enzyme. Such short-term adaptations include a highly specific multichromosome aneuploidy and large changes in ribosomal gene transcription. While aneuploid ulp2Δ cells survive, they suffer severe defects in growth and stress resistance. Over many generations, euploidy is restored, transcriptional programs are adjusted, and specific genetic changes that compensate for the loss of the SUMO protease are observed. These long-term adapted cells grow at normal rates with no detectable defects in stress resistance. In this review, we examine the connections between SUMO and cellular adaptive mechanisms more broadly.

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Section: The Ulp2 Sumo Protease and Adaptations To Its Lossmentioning

confidence: 99%

SUMO and cellular adaptive mechanisms

2020

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“…Recently, we reported that acute loss of Ulp2 leads to aneuploidy, specifically, a double disomy of chromosome I (ChrI) and ChrXII, an adaptive mechanism that compensates for a severely dysregulated SUMO system 18 . Increased dosage of two ChrI genes, CLN3 , encoding a G 1 cyclin, and CCR4 , encoding the catalytic deadenylase subunit of the Ccr4-Not complex, were shown to drive the ChrI disomy 18,19 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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