title: Loss of the SUMO protease Ulp2 triggers a specific multichromosome aneuploidy.
abstract: Post-translational protein modification by the small ubiquitin-related modifier (SUMO) regulates numerous cellular pathways, including transcription, cell division, and genome maintenance. The SUMO protease Ulp2 modulates many of these SUMO-dependent processes in budding yeast. From whole-genome RNA sequencing (RNA-seq), we unexpectedly discovered that cells lacking Ulp2 display a twofold increase in transcript levels across two particular chromosomes: chromosome I (ChrI) and ChrXII. This is due to the two chromosomes being present at twice their normal copy number. An abnormal number of chromosomes, termed aneuploidy, is usually deleterious. However, development of specific aneuploidies allows rapid adaptation to cellular stresses, and aneuploidy characterizes most human tumors. Extra copies of ChrI and ChrXII appear quickly following loss of active Ulp2 and can be eliminated following reintroduction of ULP2, suggesting that aneuploidy is a reversible adaptive mechanism to counteract loss of the SUMO protease. Importantly, increased dosage of two genes on ChrI-CLN3 and CCR4, encoding a G1-phase cyclin and a subunit of the Ccr4-Not deadenylase complex, respectively-suppresses ulp2Δ aneuploidy, suggesting that increased levels of these genes underlie the aneuploidy induced by Ulp2 loss. Our results reveal a complex aneuploidy mechanism that adapts cells to loss of the SUMO protease Ulp2.
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA;
authors: Hong-Yeoul
authors: HY
authors: Ryu
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA;
authors: Nicole R
authors: NR
authors: Wilson
authors: Yale Center for Genome Analysis, Yale University, New Haven, Connecticut 06520, USA;
authors: Sameet
authors: S
authors: Mehta
authors: Department of Immunobiology, Yale University, New Haven, Connecticut 06520, USA.
authors: Soo Seok
authors: SS
authors: Hwang
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA;
authors: Mark
authors: M
authors: Hochstrasser
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000782:Aneuploidy; D002453:Cell Cycle / Q000235:genetics; D015825:Chromosomes, Fungal / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D018628:Gene Dosage / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D010450:Endopeptidases; C405949:ULP2 protein, S cerevisiae
keywords: Ccr4; Cln3; SUMO; Ulp2; aneuploidy; protease