Karyotypic Determinants of Chromosome Instability in Aneuploid Budding Yeast

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Recent studies in cancer cells and budding yeast demonstrated that aneuploidy, the state of having abnormal chromosome numbers, correlates with elevated chromosome instability (CIN), i.e. the propensity of gaining and losing chromosomes at a high frequency. Here we have investigated ploidy -⁠ and chromosome-specific determinants underlying aneuploidy-induced CIN by observing karyotype dynamics in fully isogenic aneuploid yeast strains with ploidies between 1N and 2N obtained through a random meiotic process. The aneuploid strains exhibited various levels of whole-chromosome instability (i.e. chromosome gains and losses). CIN correlates with cellular ploidy in an unexpected way: cells with a chromosomal content close to the haploid state are significantly more stable than cells displaying an apparent ploidy between 1.5 and 2N. We propose that the capacity for accurate chromosome segregation by the mitotic system does not scale continuously with an increasing number of chromosomes, but may occur via discrete steps each time a full set of chromosomes is added to the genome. On top of such general ploidy-related effect, CIN is also associated with the presence of specific aneuploid chromosomes as well as dosage imbalance between specific chromosome pairs. Our findings potentially help reconcile the divide between gene-centric versus genome-centric theories in cancer evolution.

Vyšlo v časopise: Karyotypic Determinants of Chromosome Instability in Aneuploid Budding Yeast. PLoS Genet 8(5): e32767. doi:10.1371/journal.pgen.1002719
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002719

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1. DunhamMJBadraneHFereaTAdamsJBrownPO 2002 Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 99 16144 16149

2. RancatiGPavelkaNFlehartyBNollATrimbleR 2008 Aneuploidy underlies rapid adaptive evolution of yeast cells deprived of a conserved cytokinesis motor. Cell 135 879 893

3. GreshamDDesaiMMTuckerCMJenqHTPaiDA 2008 The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast. PLoS Genet 4 e1000303 doi:10.1371/journal.pgen.1000303

4. SelmeckiAForcheABermanJ 2006 Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313 367 370

5. SelmeckiAGerami-NejadMPaulsonCForcheABermanJ 2008 An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1. Mol Microbiol 68 624 641

6. YachidaSJonesSBozicIAntalTLearyR 2010 Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467 1114 1117

7. GreenmanCStephensPSmithRDalglieshGLHunterC 2007 Patterns of somatic mutation in human cancer genomes. Nature 446 153 158

8. HanahanDWeinbergRA 2011 Hallmarks of cancer: the next generation. Cell 144 646 674

9. HengHHStevensJBBremerSWYeKJLiuG 2010 The evolutionary mechanism of cancer. J Cell Biochem 109 1072 1084

10. HengHH 2009 The genome-centric concept: resynthesis of evolutionary theory. Bioessays 31 512 525

11. HengHHBremerSWStevensJBYeKJLiuG 2009 Genetic and epigenetic heterogeneity in cancer: a genome-centric perspective. J Cell Physiol 220 538 547

12. HahnWCCounterCMLundbergASBeijersbergenRLBrooksMW 1999 Creation of human tumour cells with defined genetic elements. Nature 400 464 468

13. LiRSonikAStindlRRasnickDDuesbergP 2000 Aneuploidy vs. gene mutation hypothesis of cancer: recent study claims mutation but is found to support aneuploidy. Proc Natl Acad Sci U S A 97 3236 3241

14. TorresEMSokolskyTTuckerCMChanLYBoselliM 2007 Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317 916 924

15. PavelkaNRancatiGZhuJBradfordWSarafAFlorensLSandersonBLiR 2010 Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 468 321 325

16. CampbellDDoctorJSFeuersangerJHDoolittleMM 1981 Differential mitotic stability of yeast disomes derived from triploid meiosis. Genetics 98 239 255

17. St CharlesJHamiltonMLPetesTD 2010 Meiotic chromosome segregation in triploid strains of Saccharomyces cerevisiae. Genetics 186 537 550

18. SheltzerJMBlankHMPfauSJTangeYGeorgeBM 2011 Aneuploidy drives genomic instability in yeast. Science 333 1026 1030

19. DuesbergPRauschCRasnickDHehlmannR 1998 Genetic instability of cancer cells is proportional to their degree of aneuploidy. Proc Natl Acad Sci U S A 95 13692 13697

20. BakhoumSFThompsonSLManningALComptonDA 2009 Genome stability is ensured by temporal control of kinetochore-microtubule dynamics. Nat Cell Biol 11 27 35

21. StorchovaZBrenemanACandeJDunnJBurbankK 2006 Genome-wide genetic analysis of polyploidy in yeast. Nature 443 541 547

22. CrawfordDCNickersonDA 2005 Definition and clinical importance of haplotypes. Annu Rev Med 56 303 320

23. AndersKRKudrnaJRKellerKEKinghornBMillerEM 2009 A strategy for constructing aneuploid yeast strains by transient nondisjunction of a target chromosome. BMC Genet 10 36

24. EspinetCde la TorreMAAldeaMHerreroE 1995 An efficient method to isolate yeast genes causing overexpression-mediated growth arrest. Yeast 11 25 32

25. DeutschbauerAMJaramilloDFProctorMKummJHillenmeyerME 2005 Mechanisms of haploinsufficiency revealed by genome-wide profiling in yeast. Genetics 169 1915 1925

26. StirlingPCBloomMSSolanki-PatilTSmithSSipahimalaniP 2011 The complete spectrum of yeast chromosome instability genes identifies candidate CIN cancer genes and functional roles for ASTRA complex components. PLoS Genet 7 e1002057 doi:10.1371/journal.pgen.1002057

27. MusacchioASalmonED 2007 The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8 379 393

28. BarnhartELDorerRKMurrayAWSchuylerSC 2011 Reduced Mad2 expression keeps relaxed kinetochores from arresting budding yeast in mitosis. Mol Biol Cell 22 2448 2457

29. ThompsonSLComptonDA 2010 Proliferation of aneuploid human cells is limited by a p53-dependent mechanism. J Cell Biol 188 369 381

30. TorresEMDephoureNPanneerselvamATuckerCMWhittakerCA 2010 Identification of aneuploidy-tolerating mutations. Cell 143 71 83

31. SpringerMWeissmanJSKirschnerMW 2010 A general lack of compensation for gene dosage in yeast. Mol Syst Biol 6 368

32. SchvartzmanJMSotilloRBenezraR 2010 Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat Rev Cancer 10 102 115

33. KimJHKangJSChanCS 1999 Sli15 associates with the ipl1 protein kinase to promote proper chromosome segregation in Saccharomyces cerevisiae. J Cell Biol 145 1381 1394

34. CheesemanIMAndersonSJwaMGreenEMKangJ 2002 Phospho-regulation of kinetochore-microtubule attachments by the Aurora kinase Ipl1p. Cell 111 163 172

35. WeaverBASilkADMontagnaCVerdier-PinardPClevelandDW 2007 Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell 11 25 36

36. BirkbakNJEklundACLiQMcClellandSEEndesfelderD 2011 Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer Res 71 3447 3452

37. Ozery-FlatoMLinhartCTrakhtenbrotLIzraeliSShamirR 2011 Large-scale analysis of chromosomal aberrations in cancer karyotypes reveals two distinct paths to aneuploidy. Genome Biol 12 R61

38. Heselmeyer-HaddadKSommerfeldKWhiteNMChaudhriNMorrisonLE 2005 Genomic amplification of the human telomerase gene (TERC) in pap smears predicts the development of cervical cancer. Am J Pathol 166 1229 1238

39. CaoYBryanTMReddelRR 2008 Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells. Cancer Sci 99 1092 1099