Maintenance of Very Long Telomeres by Recombination in the Kluyveromyces lactis stn1-M1 Mutant Involves Extreme Telomeric Turnover, Telomeric Circles, and Concerted Telomeric Amplification

REFERENCES

• Bailey SM, Brenneman MA, Goodwin EH. 2004. Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells. Nucleic Acids Res. 32:3743–3751.
   PubMed Web of Science ®Google Scholar
• Basenko E, Topcu Z, McEachern MJ. 2011. Recombination can either help maintain very short telomeres or generate longer telomeres in yeast cells with weak telomerase activity. Eukaryot. Cell 10:1131–1142.
   PubMedGoogle Scholar
• Basenko EY, Cesare AJ, Iyer S, Griffith JD, McEachern MJ. 2010. Telomeric circles are abundant in the stn1-M1 mutant that maintains its telomeres through recombination. Nucleic Acids Res. 38:182–189.
   PubMedGoogle Scholar
• Bechard LH, Butuner BD, Peterson GJ, Topcu Z, McEachern MJ. 2009. Mutant telomeric repeats in yeast can disrupt the negative regulation of recombination-mediated telomere maintenance and create an alternative lengthening of telomeres-like phenotype. Mol. Cell. Biol. 29:626–639.
   PubMed Web of Science ®Google Scholar
• Bechard LH, Jamieson N, McEachern MJ. 2011. Recombination can cause telomere elongations as well as truncations deep within telomeres in wild-type Kluyveromyces lactis cells. Eukaryot. Cell 10:226–236.
   PubMedGoogle Scholar
• Bechter OE, Zou Y, Walker W, Wright WE, Shay JW. 2004. Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition. Cancer Res. 64:3444–3451.
   PubMed Web of Science ®Google Scholar
• Becker DM, Lundblad V. 1997. Introduction of DNA into yeast cells, p 13.7.5–13.7.7, Curr. Protoc. Mol. Biol., 4th ed, vol III. John Wiley & Sons, Inc. Hoboken, NJ.
   Google Scholar
• Beverley SM. 1988. Characterization of the ‘unusual’ mobility of large circular DNAs in pulsed field-gradient electrophoresis. Nucleic Acids Res. 16:925–939.
   PubMedGoogle Scholar
• Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR. 1997. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat. Med. 3:1271–1274.
   PubMed Web of Science ®Google Scholar
• Carter SD, Iyer S, Xu J, McEachern MJ, Astrom SU. 2007. The role of nonhomologous end-joining components in telomere metabolism in Kluyveromyces lactis. Genetics 175:1035–1045.
   PubMedGoogle Scholar
• Cerone MA, Autexier C, Londono-Vallejo JA, Bacchetti S. 2005. A human cell line that maintains telomeres in the absence of telomerase and of key markers of ALT. Oncogene 24:7893–7901.
   PubMed Web of Science ®Google Scholar
• Cesare AJ, Griffith JD. 2004. Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops. Mol. Cell. Biol. 24:9948–9957.
   PubMed Web of Science ®Google Scholar
• Cesare AJ, Groff-Vindman C, Compton S, McEachern MJ, Griffith JD. 2008. Telomere loops and homologous recombination-dependent telomeric circles in a Kluyveromyces lactis telomere mutant strain. Mol. Cell. Biol. 28:20–29.
   PubMed Web of Science ®Google Scholar
• Cesare AJ, Reddel RR. 2010. Alternative lengthening of telomeres: models, mechanisms and implications. Nat. Rev. Genet. 11:319–330.
   PubMed Web of Science ®Google Scholar
• Cesare AJ, Reddel RR. 2008. Telomere uncapping and alternative lengthening of telomeres. Mech. Ageing Dev. 129:99–108.
   PubMedGoogle Scholar
• Chang M, Dittmar JC, Rothstein R. 2011. Long telomeres are preferentially extended during recombination-mediated telomere maintenance. Nat. Struct. Mol. Biol. 18:451–456.
   PubMed Web of Science ®Google Scholar
• Chen Q, Ijpma A, Greider CW. 2001. Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events. Mol. Cell. Biol. 21:1819–1827.
   PubMed Web of Science ®Google Scholar
• Chen XJ. 1996. Low- and high-copy-number shuttle vectors for replication in the budding yeast Kluyveromyces lactis. Gene 172:131–136.
   PubMedGoogle Scholar
• Church GM, Gilbert W. 1984. Genomic sequencing. Proc. Natl. Acad. Sci. U. S. A. 81:1991–1995.
   PubMed Web of Science ®Google Scholar
• Cohen H, Sinclair DA. 2001. Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase. Proc. Natl. Acad. Sci. U. S. A. 98:3174–3179.
   PubMedGoogle Scholar
• Compton SA, Choi JH, Cesare AJ, Ozgur S, Griffith JD. 2007. Xrcc3 and Nbs1 are required for the production of extrachromosomal telomeric circles in human alternative lengthening of telomere cells. Cancer Res. 67:1513–1519.
   PubMedGoogle Scholar
• Dunham MA, Neumann AA, Fasching CL, Reddel RR. 2000. Telomere maintenance by recombination in human cells. Nat. Genet. 26:447–450.
   PubMed Web of Science ®Google Scholar
• Fairhead C, Dujon B. 2006. Structure of Kluyveromyces lactis subtelomeres: duplications and gene content. FEMS Yeast Res. 6:428–441.
   PubMedGoogle Scholar
• Fasching CL, Bower K, Reddel RR. 2005. Telomerase-independent telomere length maintenance in the absence of alternative lengthening of telomeres-associated promyelocytic leukemia bodies. Cancer Res. 65:2722–2729.
   PubMedGoogle Scholar
• Fire A, Xu SQ. 1995. Rolling replication of short DNA circles. Proc. Natl. Acad. Sci. U. S. A. 92:4641–4645.
   PubMed Web of Science ®Google Scholar
• Gao H, Cervantes RB, Mandell EK, Otero JH, Lundblad V. 2007. RPA-like proteins mediate yeast telomere function. Nat. Struct. Mol. Biol. 14:208–214.
   PubMed Web of Science ®Google Scholar
• Grandin N, Charbonneau M. 2003. The Rad51 pathway of telomerase-independent maintenance of telomeres can amplify TG1-3 sequences in yku and cdc13 mutants of Saccharomyces cerevisiae. Mol. Cell. Biol. 23:3721–3734.
   PubMedGoogle Scholar
• Grandin N, Charbonneau M. 2009. Telomerase- and Rad52-independent immortalization of budding yeast by an inherited-long-telomere pathway of telomeric repeat amplification. Mol. Cell. Biol. 29:965–985.
   PubMedGoogle Scholar
• Grandin N, Damon C, Charbonneau M. 2000. Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Mol. Cell. Biol. 20:8397–8408.
   PubMedGoogle Scholar
• Grandin N, Damon C, Charbonneau M. 2001. Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination. EMBO J. 20:6127–6139.
   PubMedGoogle Scholar
• Grandin N, Damon C, Charbonneau M. 2001. Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13. EMBO J. 20:1173–1183.
   PubMed Web of Science ®Google Scholar
• Grandin N, Reed SI, Charbonneau M. 1997. Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13. Genes Dev. 11:512–527.
   PubMed Web of Science ®Google Scholar
• Groff-Vindman C, Cesare AJ, Natarajan S, Griffith JD, McEachern MJ. 2005. Recombination at long mutant telomeres produces tiny single- and double-stranded telomeric circles. Mol. Cell. Biol. 25:4406–4412.
   PubMedGoogle Scholar
• Hartig JS, Kool ET. 2004. Small circular DNAs for synthesis of the human telomere repeat: varied sizes, structures and telomere-encoding activities. Nucleic Acids Res. 32:e152. https://doi.org/10.1093/nar/gnh149.
   PubMedGoogle Scholar
• Henson JD, et al. 2009. DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity. Nat. Biotechnol. 27:1181–1185.
   PubMed Web of Science ®Google Scholar
• Henson JD, Neumann AA, Yeager TR, Reddel RR. 2002. Alternative lengthening of telomeres in mammalian cells. Oncogene 21:598–610.
   PubMed Web of Science ®Google Scholar
• Hoffman CS. 1997. Preparation of yeast DNA, p 13.11.1–13.11.4, Curr. Protoc. Mol. Biol. John Wiley & Sons, Inc., Hoboken, NJ.
   Google Scholar
• Iyer S, Chadha AD, McEachern MJ. 2005. A mutation in the STN1 gene triggers an alternative lengthening of telomere-like runaway recombinational telomere elongation and rapid deletion in yeast. Mol. Cell. Biol. 25:8064–8073.
   PubMedGoogle Scholar
• Jeyapalan JN, Mendez-Bermudez A, Zaffaroni N, Dubrova YE, Royle NJ. 2008. Evidence for alternative lengthening of telomeres in liposarcomas in the absence of ALT-associated PML bodies. Int. J. Cancer 122:2414–2421.
   PubMed Web of Science ®Google Scholar
• Jiang WQ, et al. 2005. Suppression of alternative lengthening of telomeres by Sp100-mediated sequestration of the MRE11/RAD50/NBS1 complex. Mol. Cell. Biol. 25:2708–2721.
   PubMedGoogle Scholar
• Jiang WQ, Zhong ZH, Henson JD, Reddel RR. 2007. Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference. Oncogene 26:4635–4647.
   PubMedGoogle Scholar
• Kegel A, Martinez P, Carter SD, Astrom SU. 2006. Genome wide distribution of illegitimate recombination events in Kluyveromyces lactis. Nucleic Acids Res. 34:1633–1645.
   PubMedGoogle Scholar
• Kim NW, et al. 1994. Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Li B, Jog SP, Reddy S, Comai L. 2008. WRN controls formation of extrachromosomal telomeric circles and is required for TRF2DeltaB-mediated telomere shortening. Mol. Cell. Biol. 28:1892–1904.
   PubMed Web of Science ®Google Scholar
• Lindstrom UM, et al. 2002. Artificial human telomeres from DNA nanocircle templates. Proc. Natl. Acad. Sci. U. S. A. 99:15953–15958.
   PubMedGoogle Scholar
• Londono-Vallejo JA, Der-Sarkissian H, Cazes L, Bacchetti S, Reddel RR. 2004. Alternative lengthening of telomeres is characterized by high rates of telomeric exchange. Cancer Res. 64:2324–2327.
   PubMed Web of Science ®Google Scholar
• Lundblad V, Blackburn EH. 1993. An alternative pathway for yeast telomere maintenance rescues est1-senescence. Cell 73:347–360.
   PubMed Web of Science ®Google Scholar
• Lustig AJ. 2003. Clues to catastrophic telomere loss in mammals from yeast telomere rapid deletion. Nat. Rev. Genet. 4:916–923.
   PubMedGoogle Scholar
• McEachern MJ, Blackburn EH. 1996. Cap-prevented recombination between terminal telomeric repeat arrays (telomere CPR) maintains telomeres in Kluyveromyces lactis lacking telomerase. Genes Dev. 10:1822–1834.
   PubMed Web of Science ®Google Scholar
• McEachern MJ, Blackburn EH. 1995. Runaway telomere elongation caused by telomerase RNA gene mutations. Nature 376:403–409.
   PubMed Web of Science ®Google Scholar
• McEachern MJ, Haber JE. 2006. Break-induced replication and recombinational telomere elongation in yeast. Annu. Rev. Biochem. 75:111–135.
   PubMed Web of Science ®Google Scholar
• McEachern MJ, Iyer S. 2001. Short telomeres in yeast are highly recombinogenic. Mol. Cell 7:695–704.
   PubMedGoogle Scholar
• Miller KM, Cooper JP. 2003. The telomere protein Taz1 is required to prevent and repair genomic DNA breaks. Mol. Cell 11:303–313.
   PubMedGoogle Scholar
• Morin GB, Cech TR. 1986. The telomeres of the linear mitochondrial DNA of Tetrahymena thermophila consist of 53 bp tandem repeats. Cell 46:873–883.
   PubMedGoogle Scholar
• Murnane JP, Sabatier L, Marder BA, Morgan WF. 1994. Telomere dynamics in an immortal human cell line. EMBO J. 13:4953–4962.
   PubMed Web of Science ®Google Scholar
• Nabetani A, Ishikawa F. 2009. Unusual telomeric DNAs in human telomerase-negative immortalized cells. Mol. Cell. Biol. 29:703–713.
   PubMed Web of Science ®Google Scholar
• Nakayama K, Kusano K, Irino N, Nakayama H. 1994. Thymine starvation-induced structural changes in Escherichia coli DNA. Detection by pulsed field gel electrophoresis and evidence for involvement of homologous recombination. J. Mol. Biol. 243:611–620.
   PubMedGoogle Scholar
• Natarajan S, Groff-Vindman C, McEachern MJ. 2003. Factors influencing the recombinational expansion and spread of telomeric tandem arrays in Kluyveromyces lactis. Eukaryot. Cell 2:1115–1127.
   PubMedGoogle Scholar
• Natarajan S, McEachern MJ. 2002. Recombinational telomere elongation promoted by DNA circles. Mol. Cell. Biol. 22:4512–4521.
   PubMed Web of Science ®Google Scholar
• Nickles K, McEachern MJ. 2004. Characterization of Kluyveromyces lactis subtelomeric sequences including a distal element with strong purine/ pyrimidine strand bias. Yeast 21:813–830.
   PubMedGoogle Scholar
• Nishitani H, Nurse P. 1995. p65cdc18 plays a major role controlling the initiation of DNA replication in fission yeast. Cell 83:397–405.
   PubMed Web of Science ®Google Scholar
• Nosek J, Rycovska A, Makhov AM, Griffith JD, Tomaska L. 2005. Amplification of telomeric arrays via rolling-circle mechanism. J. Biol. Chem. 280:10840–10845.
   PubMedGoogle Scholar
• Nugent CI, et al. 1998. Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr. Biol. 8:657–660.
   PubMed Web of Science ®Google Scholar
• Nugent CI, Hughes TR, Lue NF, Lundblad V. 1996. Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance. Science 274:249–252.
   PubMedGoogle Scholar
• Perrem K, Colgin LM, Neumann AA, Yeager TR, Reddel RR. 2001. Coexistence of alternative lengthening of telomeres and telomerase in hTERT-transfected GM847 cells. Mol. Cell. Biol. 21:3862–3875.
   PubMed Web of Science ®Google Scholar
• Petit MA, Mesas JM, Noirot P, Morel-Deville F, Ehrlich SD. 1992. Induction of DNA amplification in the Bacillus subtilis chromosome. EMBO J. 11:1317–1326.
   PubMedGoogle Scholar
• Philippsen P, Stotz A, Scherf C. 1991. DNA of Saccharomyces cerevisiae. Methods Enzymol. 194:169–182.
   PubMed Web of Science ®Google Scholar
• Potts PR, Yu H. 2007. The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins. Nat. Struct. Mol. Biol. 14:581–590.
   PubMed Web of Science ®Google Scholar
• Price CM, et al. 2010. Evolution of CST function in telomere maintenance. Cell Cycle 9:3157–3165.
   PubMed Web of Science ®Google Scholar
• Puglisi A, Bianchi A, Lemmens L, Damay P, Shore D. 2008. Distinct roles for yeast Stn1 in telomere capping and telomerase inhibition. EMBO J. 27:2328–2339.
   PubMed Web of Science ®Google Scholar
• Rogan EM, et al. 1995. Alterations in p53 and p16INK4 expression and telomere length during spontaneous immortalization of Li-Fraumeni syndrome fibroblasts. Mol. Cell. Biol. 15:4745–4753.
   PubMed Web of Science ®Google Scholar
• Roy J, Fulton TB, Blackburn EH. 1998. Specific telomerase RNA residues distant from the template are essential for telomerase function. Genes Dev. 12:3286–3300.
   PubMedGoogle Scholar
• Sabatier L, Ricoul M, Pottier G, Murnane JP. 2005. The loss of a single telomere can result in instability of multiple chromosomes in a human tumor cell line. Mol. Cancer Res. 3:139–150.
   PubMed Web of Science ®Google Scholar
• Sambrook J, Russell DW. 2001. Preparation of DNA for pulsed-field gel electrophoresis: isolation of intact DNA from yeast, p 5.65–5.67. InSambrook J, Russell DW (ed), Molecular cloning: a laboratory manual, 3rd ed, vol 1. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
   Google Scholar
• Stewart SA, Weinberg RA. 2006. Telomeres: cancer to human aging. Annu. Rev. Cell Dev. Biol. 22:531–557.
   PubMed Web of Science ®Google Scholar
• Sun J, et al. 2009. Stn1-Ten1 is an Rpa2-Rpa3-like complex at telomeres. Genes Dev. 23:2900–2914.
   PubMed Web of Science ®Google Scholar
• Takahashi K, et al. 2011. Fission yeast Pot1 and RecQ helicase are required for efficient chromosome segregation. Mol. Cell. Biol. 31:495–506.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Tomaska L, Nosek J, Makhov AM, Pastorakova A, Griffith JD. 2000. Extragenomic double-stranded DNA circles in yeast with linear mitochondrial genomes: potential involvement in telomere maintenance. Nucleic Acids Res. 28:4479–4487.
   PubMedGoogle Scholar
• Topcu Z, Nickles K, Davis C, McEachern MJ. 2005. Abrupt disruption of capping and a single source for recombinationally elongated telomeres in Kluyveromyces lactis. Proc. Natl. Acad. Sci. U. S. A. 102:3348–3353.
   PubMedGoogle Scholar
• Tsai YL, Tseng SF, Chang SH, Lin CC, Teng SC. 2002. Involvement of replicative polymerases, Tel1p, Mec1p, Cdc13p, and the Ku complex in telomere-telomere recombination. Mol. Cell. Biol. 22:5679–5687.
   PubMed Web of Science ®Google Scholar
• van Steensel B, Smogorzewska A, de Lange T. 1998. TRF2 protects human telomeres from end-to-end fusions. Cell 92:401–413.
   PubMed Web of Science ®Google Scholar
• Vega LR, et al. 2007. Sensitivity of yeast strains with long G-tails to levels of telomere-bound telomerase. PLoS Genet. 3:e105. https://doi.org/10.1371/journal.pgen.0030105.
   PubMedGoogle Scholar
• Wang RC, Smogorzewska A, de Lange T. 2004. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119:355–368.
   PubMed Web of Science ®Google Scholar
• Wray LVJr, Witte MM, Dickson RC, Riley MI. 1987. Characterization of a positive regulatory gene, LAC9, that controls induction of the lactose-galactose regulon of Kluyveromyces lactis: structural and functional relationships to GAL4 of Saccharomyces cerevisiae. Mol. Cell. Biol. 7:1111–1121.
   PubMedGoogle Scholar
• Yeager TR, et al. 1999. Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. Cancer Res. 59:4175–4179.
   PubMed Web of Science ®Google Scholar
• Zellinger B, Akimcheva S, Puizina J, Schirato M, Riha K. 2007. Ku suppresses formation of telomeric circles and alternative telomere lengthening in Arabidopsis. Mol. Cell 27:163–169.
   PubMed Web of Science ®Google Scholar
• Zeng S, et al. 2009. Telomere recombination requires the MUS81 endonuclease. Nat. Cell Biol. 11:616–623.
   PubMed Web of Science ®Google Scholar
• Zhong ZH, et al. 2007. Disruption of telomere maintenance by depletion of the MRE11/RAD50/NBS1 complex in cells that use alternative lengthening of telomeres. J. Biol. Chem. 282:29314–29322.
   PubMed Web of Science ®Google Scholar