Aneuploidy as a mechanism of adaptation to telomerase insufficiency

Current Genetics - Tập 62 - Trang 557-564 - 2016
Caroline Millet1, Svetlana Makovets1
1School of Biological Sciences, Institute of Cell Biology, University of Edinburgh, Edinburgh, UK

Tóm tắt

Cells’ survival is determined by their ability to adapt to constantly changing environment. Adaptation responses involve global changes in transcription, translation, and posttranslational modifications of proteins. In recent years, karyotype changes in adapting populations of single cell organisms have been reported in a number of studies. More recently, we have described aneuploidy as an adaptation mechanism used by populations of budding yeast Saccharomyces cerevisiae to survive telomerase insufficiency induced by elevated growth temperature. Genetic evidence suggests that telomerase insufficiency is caused by decreased levels of the telomerase catalytic subunit Est2. Here, we present experiments arguing that the underlying cause of this phenomenon may be within the telomerase RNA TLC1: changes in the expression of TLC1 as well as mutations in the TLC1 template region affect telomere length equilibrium and the temperature threshold for the induction of telomerase insufficiency. We discuss what lies at the root of telomerase insufficiency, how cell populations overcome it through aneuploidy and whether reversible aneuploidy could be an adaptation mechanism for a variety of environmental stresses.

Tài liệu tham khảo

As IJ, Greider CW (2003) Short telomeres induce a DNA damage response in Saccharomyces cerevisiae. Mol Biol Cell 14:987–1001. doi:10.1091/mbc.02-04-0057 Bai L, Charvin G, Siggia ED, Cross FR (2010) Nucleosome-depleted regions in cell-cycle-regulated promoters ensure reliable gene expression in every cell cycle. Dev Cell 18:544–555. doi:10.1016/j.devcel.2010.02.007 Broach JR (2012) Nutritional control of growth and development in yeast. Genetics 192:73–105. doi:10.1534/genetics.111.135731 Caspeta L, Chen Y, Ghiaci P, Feizi A, Buskov S, Hallstrom BM, Petranovic D, Nielsen J (2014) Biofuels. Altered sterol composition renders yeast thermotolerant. Science 346:75–78. doi:10.1126/science.1258137 Chappell AS, Lundblad V (2004) Structural elements required for association of the Saccharomyces cerevisiae telomerase RNA with the Est2 reverse transcriptase. Mol Cell Biol 24:7720–7736. doi:10.1128/MCB.24.17.7720-7736.2004 Chen G, Rubinstein B, Li R (2012) Whole chromosome aneuploidy: big mutations drive adaptation by phenotypic leap. BioEssays 34:893–900. doi:10.1002/bies.201200069 Dragon F, Gallagher JE, Compagnone-Post PA, Mitchell BM, Porwancher KA, Wehner KA, Wormsley S, Settlage RE, Shabanowitz J, Osheim Y, Beyer AL, Hunt DF, Baserga SJ (2002) A large nucleolar U3 ribonucleoprotein required for 18S ribosomal RNA biogenesis. Nature 417:967–970. doi:10.1038/nature00769 Gasch AP (2007) Comparative genomics of the environmental stress response in ascomycete fungi. Yeast 24:961–976. doi:10.1002/yea.1512 Gomes NM, Shay JW, Wright WE (2010) Telomere biology in Metazoa. FEBS Lett 584:3741–3751. doi:10.1016/j.febslet.2010.07.031 Greider CW, Blackburn EH (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43:405–413 Greider CW, Blackburn EH (1987) The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell 51:887–898 Krajewski SS, Narberhaus F (2014) Temperature-driven differential gene expression by RNA thermosensors. Biochim Biophys Acta 1839:978–988. doi:10.1016/j.bbagrm.2014.03.006 Le S, Moore JK, Haber JE, Greider CW (1999) RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase. Genetics 152:143–152 Lundblad V, Blackburn EH (1993) An alternative pathway for yeast telomere maintenance rescues est1-senescence. Cell 73:347–360 Lundblad V, Szostak JW (1989) A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57:633–643 Makovets S, Herskowitz I, Blackburn EH (2004) Anatomy and dynamics of DNA replication fork movement in yeast telomeric regions. Mol Cell Biol 24:4019–4031 Makovets S, Williams TL, Blackburn EH (2008) The telotype defines the telomere state in Saccharomyces cerevisiae and is inherited as a dominant non-Mendelian characteristic in cells lacking telomerase. Genetics 178:245–257. doi:10.1534/genetics.107.083030 Millet C, Ausiannikava D, Le Bihan T, Granneman S, Makovets S (2015) Cell populations can use aneuploidy to survive telomerase insufficiency. Nat Commun 6:8664. doi:10.1038/ncomms9664 Moyzis RK, Buckingham JM, Cram LS, Dani M, Deaven LL, Jones MD, Meyne J, Ratliff RL, Wu JR (1988) A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA 85:6622–6626 Niederer RO, Zappulla DC (2015) Refined secondary-structure models of the core of yeast and human telomerase RNAs directed by SHAPE. RNA 21:1053 Pfingsten JS, Goodrich KJ, Taabazuing C, Ouenzar F, Chartrand P, Cech TR (2012) Mutually exclusive binding of telomerase RNA and DNA by Ku alters telomerase recruitment model. Cell 148:922–932. doi:10.1016/j.cell.2012.01.033 Prescott J, Blackburn EH (1997) Telomerase RNA mutations in Saccharomyces cerevisiae alter telomerase action and reveal nonprocessivity in vivo and in vitro. Genes Dev 11:528–540 Romano GH, Harari Y, Yehuda T, Podhorzer A, Rubinstein L, Shamir R, Gottlieb A, Silberberg Y, Pe’er D, Ruppin E, Sharan R, Kupiec M (2013) Environmental stresses disrupt telomere length homeostasis. PLoS Genet 9:e1003721. doi:10.1371/journal.pgen.1003721 Shampay J, Szostak JW, Blackburn EH (1984) DNA sequences of telomeres maintained in yeast. Nature 310:154–157 Shore D (1997) Telomere length regulation: getting the measure of chromosome ends. Biol Chem 378:591–597 Simonicova L, Dudekova H, Ferenc J, Prochazkova K, Nebohacova M, Dusinsky R, Nosek J, Tomaska L (2015) Saccharomyces cerevisiae as a model for the study of extranuclear functions of mammalian telomerase. Curr Genet 61:517–527. doi:10.1007/s00294-014-0472-8 Singer MS, Gottschling DE (1994) TLC1: template RNA component of Saccharomyces cerevisiae telomerase. Science 266:404–409 Teng SC, Zakian VA (1999) Telomere–telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. Mol Cell Biol 19:8083–8093 Tucey TM, Lundblad V (2014) Regulated assembly and disassembly of the yeast telomerase quaternary complex. Genes Dev 28:2077–2089. doi:10.1101/gad.246256.114 Ungar L, Harari Y, Toren A, Kupiec M (2011) Tor complex 1 controls telomere length by affecting the level of Ku. Curr Biol 21:2115–2120. doi:10.1016/j.cub.2011.11.024 Vijayraghavan U, Company M, Abelson J (1989) Isolation and characterization of pre-mRNA splicing mutants of Saccharomyces cerevisiae. Genes Dev 3:1206–1216 Warner JR (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem Sci 24:437–440 Yona AH, Manor YS, Herbst RH, Romano GH, Mitchell A, Kupiec M, Pilpel Y, Dahan O (2012) Chromosomal duplication is a transient evolutionary solution to stress. Proc Natl Acad Sci USA 109:21010–21015. doi:10.1073/pnas.1211150109