The CCR4-NOT Complex Is Implicated in the Viability of Aneuploid Yeasts
To identify the genes required to sustain aneuploid viability, we screened a deletion library of non-essential genes in the fission yeast Schizosaccharomyces pombe, in which most types of aneuploidy are eventually lethal to the cell. Aneuploids remain viable for a period of time and can form colonies by reducing the extent of the aneuploidy. We hypothesized that a reduction in colony formation efficiency could be used to screen for gene deletions that compromise aneuploid viability. Deletion mutants were used to measure the effects on the viability of spores derived from triploid meiosis and from a chromosome instability mutant. We found that the CCR4-NOT complex, an evolutionarily conserved general regulator of mRNA turnover, and other related factors, including poly(A)-specific nuclease for mRNA decay, are involved in aneuploid viability. Defective mutations in CCR4-NOT complex components in the distantly related yeast Saccharomyces cerevisiae also affected the viability of spores produced from triploid cells, suggesting that this complex has a conserved role in aneuploids. In addition, our findings suggest that the genes required for homologous recombination repair are important for aneuploid viability.
Vyšlo v časopise:
The CCR4-NOT Complex Is Implicated in the Viability of Aneuploid Yeasts. PLoS Genet 8(6): e32767. doi:10.1371/journal.pgen.1002776
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002776
Souhrn
To identify the genes required to sustain aneuploid viability, we screened a deletion library of non-essential genes in the fission yeast Schizosaccharomyces pombe, in which most types of aneuploidy are eventually lethal to the cell. Aneuploids remain viable for a period of time and can form colonies by reducing the extent of the aneuploidy. We hypothesized that a reduction in colony formation efficiency could be used to screen for gene deletions that compromise aneuploid viability. Deletion mutants were used to measure the effects on the viability of spores derived from triploid meiosis and from a chromosome instability mutant. We found that the CCR4-NOT complex, an evolutionarily conserved general regulator of mRNA turnover, and other related factors, including poly(A)-specific nuclease for mRNA decay, are involved in aneuploid viability. Defective mutations in CCR4-NOT complex components in the distantly related yeast Saccharomyces cerevisiae also affected the viability of spores produced from triploid cells, suggesting that this complex has a conserved role in aneuploids. In addition, our findings suggest that the genes required for homologous recombination repair are important for aneuploid viability.
Zdroje
1. HassoldTHallHHuntP 2007 The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet 16 R203 208
2. KopsGJWeaverBAClevelandDW 2005 On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5 773 785
3. StorchovaZKufferC 2008 The consequences of tetraploidy and aneuploidy. J Cell Sci 121 3859 3866
4. HuettelBKreilDPMatzkeMMatzkeAJM 2008 Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana. PLoS Genet 4 doi:10.1371/journal.pgen.1000226 e1000226
5. LeitchARLeitchIJ 2008 Genomic plasticity and the diversity of polyploid plants. Science 320 481 483
6. TorresEMWilliamsBRAmonA 2008 Aneuploidy: cells losing their balance. Genetics 179 737 746
7. WilliamsBRPrabhuVRHunterKEGlazierCMWhittakerCA 2008 Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells. Science 322 703 709
8. NiwaOTangeYKurabayashiA 2006 Growth arrest and chromosome instability in aneuploid yeast. Yeast 23 937 950
9. TorresEMSokolskyTTuckerCMChanLYBoselliM 2007 Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317 916 924
10. SheltzerJMBlankHMPfauSJTangeYGeorgeBM 2011 Aneuploidy drives genomic instability in yeast. Science 333 1026 1030
11. ParryEMCoxBS 1970 The tolerance of aneuploidy in yeast. Genet Res 16 333 340
12. CampbellDDoctorJSFeuersangerJHDoolittleMM 1981 Differential mitotic stability of yeast disomes derived from triploid meiosis. Genetics 98 239 255
13. PavelkaNRancatiGZhuJBradfordWDSarafA 2010 Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 468 321 325
14. TorresEMDephoureNPanneerselvamATuckerCMWhittakerCA 2010 Identification of aneuploidy-tolerating mutations. Cell 143 71 83
15. NiwaOYanagidaM 1985 Triploid meiosis and aneuploidy in Schizosaccharomyces pombe: an unstable aneuploid disomic for chromosome III. Curr Genet 9 463 470
16. KimDUHaylesJKimDWoodVParkHO 2010 Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe. Nat Biotechnol 28 617 623
17. TangeYNiwaO 2007 Novel mad2 alleles isolated in a Schizosaccharomyces pombe γ-tubulin mutant are defective in metaphase arrest activity, but remain functional for chromosome stability in unperturbed mitosis. Genetics 175 1571 1584
18. DenisCLChenJ 2003 The CCR4-NOT complex plays diverse roles in mRNA metabolism. Prog Nucleic Acid Res Mol Biol 73 221 250
19. CollartMA 2003 Global control of gene expression in yeast by the Ccr4-Not complex. Gene 313 1 16
20. CollartMATimmersHT 2004 The eukaryotic Ccr4-Not complex: a regulatory platform integrating mRNA metabolism with cellular signaling pathways? Prog Nucleic Acid Res Mol Biol 77 289 322
21. CuiYRamnarainDBChiangYCDingLHMcMahonJS 2008 Genome wide expression analysis of the CCR4-NOT complex indicates that it consists of three modules with the NOT module controlling SAGA-responsive genes. Mol Genet Genomics 279 323 337
22. AzzouzNPanasenkoOODeluenCHsiehJTheilerG 2009 Specific roles for the Ccr4-Not complex subunits in expression of the genome. RNA 15 377 383
23. WattSMataJLopez-MauryLMargueratSBurnsG 2008 urg1: a uracil-regulatable promoter system for fission yeast with short induction and repression times. PLoS ONE 3 doi:10.1371/journal.pone.0001428 e1428
24. LoidlJ 1995 Meiotic chromosome pairing in triploid and tetraploid Saccharomyces cerevisiae. Genetics 139 1511 1520
25. GrishchukALKohliJ 2003 Five RecA-like proteins of Schizosaccharomyces pombe are involved in meiotic recombination. Genetics 165 1031 1043
26. RajiHHartsuikerE 2006 Double-strand break repair and homologous recombination in Schizosaccharomyces pombe. Yeast 23 963 976
27. DuLLNakamuraTMMoserBARussellP 2003 Retention but not recruitment of Crb2 at double-strand breaks requires Rad1 and Rad3 complexes. Mol Cell Biol 23 6150 6158
28. PruddenJEvansJSHusseySPDeansBO'NeillP 2003 Pathway utilization in response to a site-specific DNA double-strand break in fission yeast. EMBO J 22 1419 1430
29. YoonJHLoveDCGuhathakurtaAHanoverJADharR 2000 Mex67p of Schizosaccharomyces pombe interacts with Rae1p in mediating mRNA export. Mol Cell Biol 20 8767 8782
30. ThakurtaAGWhalenWAYoonJHBharathiAKozakL 2002 Crp79, like Mex67p, is an auxiliary mRNA export factor in Schizosaccharomyces pombe. Mol Biol Cell 13 2571 2584
31. SipiczkiM 2000 Where does fission yeast sit on the tree of life? Genome Biol 1 reviews 1011.1 1011.4
32. FitzpatrickDALogueMEStajichJEButlerG 2006 A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis. BMC Evol Biol 6 99
33. AzzouzNPanasenkoOOColauGCollartMA 2009 The CCR4-NOT complex physically and functionally interacts with TRAMP and the nuclear exosome. PLoS ONE 4 doi:10.1371/journal.pone.0006760 e6760
34. AlbertTKHanzawaHLegtenbergYIde RuweMJvan den HeuvelFA 2002 Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex. EMBO J 21 355 364
35. PanasenkoOLandrieuxEFeuermannMFinkaAPaquetN 2006 The yeast Ccr4-Not complex controls ubiquitination of the nascent-associated polypeptide (NAC-EGD) complex. J Biol Chem 281 31389 31398
36. GarcesRGGillonWPaiEF 2007 Atomic model of human Rcd-1 reveals an armadillo-like-repeat protein with in vitro nucleic acid binding properties. Protein Sci 16 176 188
37. AndersenKRJonstrupATVanLBBrodersenDE 2009 The activity and selectivity of fission yeast Pop2p are affected by a high affinity for Zn2+ and Mn2+ in the active site. RNA 15 850 861
38. LauNCKolkmanAvan SchaikFMMulderKWPijnappelWW 2009 Human Ccr4-Not complexes contain variable deadenylase subunits. Biochem J 422 443 453
39. TuckerMValencia-SanchezMAStaplesRRChenJDenisCL 2001 The transcription factor associated Ccr4 and Caf1 proteins are components of the major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae. Cell 104 377 386
40. JonstrupATAndersenKRVanLBBrodersenDE 2007 The 1.4-Å crystal structure of the S. pombe Pop2p deadenylase subunit unveils the configuration of an active enzyme. Nucleic Acids Res 35 3153 3164
41. TanakaKChangHLKagamiAWatanabeY 2009 CENP-C functions as a scaffold for effectors with essential kinetochore functions in mitosis and meiosis. Dev Cell 17 334 343
42. BennettCBLewisLKKarthikeyanGLobachevKSJinYH 2001 Genes required for ionizing radiation resistance in yeast. Nat Genet 29 426 434
43. WestmorelandTJMarksJROlsonJAJrThompsonEMResnickMA 2004 Cell cycle progression in G1 and S phases is CCR4 dependent following ionizing radiation or replication stress in Saccharomyces cerevisiae. Eukaryot Cell 3 430 446
44. TakahashiSKontaniKArakiYKatadaT 2007 Caf1 regulates translocation of ribonucleotide reductase by releasing nucleoplasmic Spd1-Suc22 assembly. Nucleic Acids Res 35 1187 1197
45. DeshpandeGPHaylesJHoeKLKimDUParkHO 2009 Screening a genome wide S. pombe deletion library identifies novel genes and pathways involved in the DNA damage response. DNA Repair (Amst) 8 672 679
46. RoseMDWinstonFHieterP 1990 Methods in yeast genetics: a laboratory course manual. Cold Spring Harbor Laboratoy Press, Cold Spring Harbor, New York
47. MorenoSKlarANurseP 1991 Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol 194 795 823
48. BählerJWuJQLongtineMSShahNGMcKenzieA3ed 1998 Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast 14 943 951
49. SatoMDhutSTodaT 2005 New drug-resistant cassettes for gene disruption and epitope tagging in Schizosaccharomyces pombe. Yeast 22 583 591
50. WoodVGwilliamRRajandreamMALyneMLyneR 2002 The genome sequence of Schizosaccharomyces pombe. Nature 415 871 880
51. LyneRBurnsGMataJPenkettCJRusticiG 2003 Whole-genome microarrays of fission yeast: characteristics, accuracy, reproducibility, and processing of array data. BMC Genomics 4 27
52. StorlazziAXuLCaoLKlecknerN 1995 Crossover and noncrossover recombination during meiosis: timing and pathway relationships. Proc Natl Acad Sci USA 92 8512 8516
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 6
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Rumors of Its Disassembly Have Been Greatly Exaggerated: The Secret Life of the Synaptonemal Complex at the Centromeres
- The NSL Complex Regulates Housekeeping Genes in
- Tipping the Balance in the Powerhouse of the Cell to “Protect” Colorectal Cancer
- Interplay between Synaptonemal Complex, Homologous Recombination, and Centromeres during Mammalian Meiosis