This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ritchie, K. B.
Right arrow Articles by Petes, T. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ritchie, K. B.
Right arrow Articles by Petes, T. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 1999, p. 6065-6075, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interactions of TLC1 (Which Encodes the RNA Subunit of Telomerase), TEL1, and MEC1 in Regulating Telomere Length in the Yeast Saccharomyces cerevisiae

Kim B. Ritchie,1 Julia C. Mallory,2 and Thomas D. Petes1,2,*

Department of Biology1 and Curriculum in Genetics and Molecular Biology,2 University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3280

Received 3 March 1999/Returned for modification 23 April 1999/Accepted 9 June 1999

In the yeast Saccharomyces cerevisiae, chromosomes terminate with a repetitive sequence [poly(TG1-3)] 350 to 500 bp in length. Strains with a mutation of TEL1, a homolog of the human gene (ATM) mutated in patients with ataxia telangiectasia, have short but stable telomeric repeats. Mutations of TLC1 (encoding the RNA subunit of telomerase) result in strains that have continually shortening telomeres and a gradual loss of cell viability; survivors of senescence arise as a consequence of a Rad52p-dependent recombination events that amplify telomeric and subtelomeric repeats. We show that a mutation in MEC1 (a gene related in sequence to TEL1 and ATM) reduces telomere length and that tel1 mec1 double mutant strains have a senescent phenotype similar to that found in tlc1 strains. As observed in tlc1 strains, survivors of senescence in the tel1 mec1 strains occur by a Rad52p-dependent amplification of telomeric and subtelomeric repeats. In addition, we find that strains with both tel1 and tlc1 mutations have a delayed loss of cell viability compared to strains with the single tlc1 mutation. This result argues that the role of Tel1p in telomere maintenance is not solely a direct activation of telomerase.


* Corresponding author. Mailing address: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280. Phone: (919) 962-1445. Fax: (919) 962-8472. E-mail: tompetes{at}emailunc.edu.


Molecular and Cellular Biology, September 1999, p. 6065-6075, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Ma, Y., Greider, C. W. (2009). Kinase-Independent Functions of TEL1 in Telomere Maintenance. Mol. Cell. Biol. 29: 5193-5202 [Abstract] [Full Text]  
  • Seidel, J. J., Anderson, C. M., Blackburn, E. H. (2008). A Novel Tel1/ATM N-Terminal Motif, TAN, Is Essential for Telomere Length Maintenance and a DNA Damage Response. Mol. Cell. Biol. 28: 5736-5746 [Abstract] [Full Text]  
  • Mori, C., Takanami, T., Higashitani, A. (2008). Maintenance of Mitochondrial DNA by the Caenorhabditis elegans ATR Checkpoint Protein ATL-1. Genetics 180: 681-686 [Abstract] [Full Text]  
  • Vernon, M., Lobachev, K., Petes, T. D. (2008). High Rates of "Unselected" Aneuploidy and Chromosome Rearrangements in tel1 mec1 Haploid Yeast Strains. Genetics 179: 237-247 [Abstract] [Full Text]  
  • Longhese, M. P. (2008). DNA damage response at functional and dysfunctional telomeres. Genes Dev. 22: 125-140 [Abstract] [Full Text]  
  • Baldo, V., Testoni, V., Lucchini, G., Longhese, M. P. (2008). Dominant TEL1-hy Mutations Compensate for Mec1 Lack of Functions in the DNA Damage Response. Mol. Cell. Biol. 28: 358-375 [Abstract] [Full Text]  
  • Chang, M., Arneric, M., Lingner, J. (2007). Telomerase repeat addition processivity is increased at critically short telomeres in a Tel1-dependent manner in Saccharomyces cerevisiae. Genes Dev. 21: 2485-2494 [Abstract] [Full Text]  
  • Viscardi, V., Bonetti, D., Cartagena-Lirola, H., Lucchini, G., Longhese, M. P. (2007). MRX-dependent DNA Damage Response to Short Telomeres. Mol. Biol. Cell 18: 3047-3058 [Abstract] [Full Text]  
  • Bianchi, A., Shore, D. (2007). Increased association of telomerase with short telomeres in yeast. Genes Dev. 21: 1726-1730 [Abstract] [Full Text]  
  • Hirano, Y., Sugimoto, K. (2007). Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends. Mol. Biol. Cell 18: 2026-2036 [Abstract] [Full Text]  
  • Reis, C. C., Campbell, J. L. (2007). Contribution of Trf4/5 and the Nuclear Exosome to Genome Stability Through Regulation of Histone mRNA Levels in Saccharomyces cerevisiae. Genetics 175: 993-1010 [Abstract] [Full Text]  
  • Grandin, N., Charbonneau, M. (2007). Control of the yeast telomeric senescence survival pathways of recombination by the Mec1 and Mec3 DNA damage sensors and RPA. Nucleic Acids Res 35: 822-838 [Abstract] [Full Text]  
  • Kedde, M., le Sage, C., Duursma, A., Zlotorynski, E., van Leeuwen, B., Nijkamp, W., Beijersbergen, R., Agami, R. (2006). Telomerase-independent Regulation of ATR by Human Telomerase RNA. J. Biol. Chem. 281: 40503-40514 [Abstract] [Full Text]  
  • Tseng, S.-F., Lin, J.-J., Teng, S.-C. (2006). The telomerase-recruitment domain of the telomere binding protein Cdc13 is regulated by Mec1p/Tel1p-dependent phosphorylation. Nucleic Acids Res 34: 6327-6336 [Abstract] [Full Text]  
  • Budd, M. E., Reis, C. C., Smith, S., Myung, K., Campbell, J. L. (2006). Evidence Suggesting that Pif1 Helicase Functions in DNA Replication with the Dna2 Helicase/Nuclease and DNA Polymerase {delta}.. Mol. Cell. Biol. 26: 2490-2500 [Abstract] [Full Text]  
  • Feldser, D., Strong, M. A., Greider, C. W. (2006). Ataxia telangiectasia mutated (Atm) is not required for telomerase-mediated elongation of short telomeres. Proc. Natl. Acad. Sci. USA 103: 2249-2251 [Abstract] [Full Text]  
  • Kirchmaier, A. L., Rine, J. (2006). Cell Cycle Requirements in Assembling Silent Chromatin in Saccharomyces cerevisiae. Mol. Cell. Biol. 26: 852-862 [Abstract] [Full Text]  
  • GREIDER, C.W. (2006). Telomerase RNA Levels Limit the Telomere Length Equilibrium. Cold Spring Harb Symp Quant Biol 71: 225-229 [Abstract]  
  • Nakada, D., Hirano, Y., Tanaka, Y., Sugimoto, K. (2005). Role of the C Terminus of Mec1 Checkpoint Kinase in Its Localization to Sites of DNA Damage. Mol. Biol. Cell 16: 5227-5235 [Abstract] [Full Text]  
  • Bi, X., Srikanta, D., Fanti, L., Pimpinelli, S., Badugu, R., Kellum, R., Rong, Y. S. (2005). Drosophila ATM and ATR checkpoint kinases control partially redundant pathways for telomere maintenance. Proc. Natl. Acad. Sci. USA 102: 15167-15172 [Abstract] [Full Text]  
  • Vespa, L., Couvillion, M., Spangler, E., Shippen, D. E. (2005). ATM and ATR make distinct contributions to chromosome end protection and the maintenance of telomeric DNA in Arabidopsis. Genes Dev. 19: 2111-2115 [Abstract] [Full Text]  
  • Chen, Y.-B., Yang, C.-P., Li, R.-X., Zeng, R., Zhou, J.-Q. (2005). Def1p Is Involved in Telomere Maintenance in Budding Yeast. J. Biol. Chem. 280: 24784-24791 [Abstract] [Full Text]  
  • Zhao, X., Blobel, G. (2005). From The Cover: A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc. Natl. Acad. Sci. USA 102: 4777-4782 [Abstract] [Full Text]  
  • York, S. J., Armbruster, B. N., Greenwell, P., Petes, T. D., York, J. D. (2005). Inositol Diphosphate Signaling Regulates Telomere Length. J. Biol. Chem. 280: 4264-4269 [Abstract] [Full Text]  
  • Toussaint, M., Dionne, I., Wellinger, R. J. (2005). Limited TTP supply affects telomere length regulation in a telomerase-independent fashion. Nucleic Acids Res 33: 704-713 [Abstract] [Full Text]  
  • Nakada, D., Hirano, Y., Sugimoto, K. (2004). Requirement of the Mre11 Complex and Exonuclease 1 for Activation of the Mec1 Signaling Pathway. Mol. Cell. Biol. 24: 10016-10025 [Abstract] [Full Text]  
  • Hao, L.-Y., Strong, M. A., Greider, C. W. (2004). Phosphorylation of H2AX at Short Telomeres in T Cells and Fibroblasts. J. Biol. Chem. 279: 45148-45154 [Abstract] [Full Text]  
  • d'Adda di Fagagna, F., Teo, S.-H., Jackson, S. P. (2004). Functional links between telomeres and proteins of the DNA-damage response. Genes Dev. 18: 1781-1799 [Abstract] [Full Text]  
  • Oikemus, S. R., McGinnis, N., Queiroz-Machado, J., Tukachinsky, H., Takada, S., Sunkel, C. E., Brodsky, M. H. (2004). Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect. Genes Dev. 18: 1850-1861 [Abstract] [Full Text]  
  • Baroni, E., Viscardi, V., Cartagena-Lirola, H., Lucchini, G., Longhese, M. P. (2004). The Functions of Budding Yeast Sae2 in the DNA Damage Response Require Mec1- and Tel1-Dependent Phosphorylation. Mol. Cell. Biol. 24: 4151-4165 [Abstract] [Full Text]  
  • Grossi, S., Puglisi, A., Dmitriev, P. V., Lopes, M., Shore, D. (2004). Pol12, the B subunit of DNA polymerase {alpha}, functions in both telomere capping and length regulation. Genes Dev. 18: 992-1006 [Abstract] [Full Text]  
  • Bah, A., Bachand, F., Clair, E., Autexier, C., Wellinger, R. J. (2004). Humanized telomeres and an attempt to express a functional human telomerase in yeast. Nucleic Acids Res 32: 1917-1927 [Abstract] [Full Text]  
  • Bai, Y., Murnane, J. P. (2003). Telomere Instability in a Human Tumor Cell Line Expressing NBS1 With Mutations at Sites Phosphorylated by ATM. Mol Cancer Res 1: 1058-1069 [Abstract] [Full Text]  
  • Bitterman, K. J., Medvedik, O., Sinclair, D. A. (2003). Longevity Regulation in Saccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin. Microbiol. Mol. Biol. Rev. 67: 376-399 [Abstract] [Full Text]  
  • Viscardi, V., Baroni, E., Romano, M., Lucchini, G., Longhese, M. P. (2003). Sudden Telomere Lengthening Triggers a Rad53-dependent Checkpoint in Saccharomyces cerevisiae. Mol. Biol. Cell 14: 3126-3143 [Abstract] [Full Text]  
  • Dahlen, M., Sunnerhagen, P., Wang, T. S.-F. (2003). Replication Proteins Influence the Maintenance of Telomere Length and Telomerase Protein Stability. Mol. Cell. Biol. 23: 3031-3042 [Abstract] [Full Text]  
  • Qi, H., Li, T.-K., Kuo, D., Nur-E-Kamal, A., Liu, L. F. (2003). Inactivation of Cdc13p Triggers MEC1-dependent Apoptotic Signals in Yeast. J. Biol. Chem. 278: 15136-15141 [Abstract] [Full Text]  
  • Hand, R. A., Jia, N., Bard, M., Craven, R. J. (2003). Saccharomyces cerevisiae Dap1p, a Novel DNA Damage Response Protein Related to the Mammalian Membrane-Associated Progesterone Receptor. Eukaryot Cell 2: 306-317 [Abstract] [Full Text]  
  • Forstemann, K., Zaug, A. J., Cech, T. R., Lingner, J. (2003). Yeast telomerase is specialized for C/A-rich RNA templates. Nucleic Acids Res 31: 1646-1655 [Abstract] [Full Text]  
  • Masrouha, N., Yang, L., Hijal, S., Larochelle, S., Suter, B. (2003). The Drosophila chk2 Gene loki Is Essential for Embryonic DNA Double-Strand-Break Checkpoints Induced in S Phase or G2. Genetics 163: 973-982 [Abstract] [Full Text]  
  • IJpma, A. S., Greider, C. W. (2003). Short Telomeres Induce a DNA Damage Response in Saccharomyces cerevisiae. Mol. Biol. Cell 14: 987-1001 [Abstract] [Full Text]  
  • Symington, L. S. (2002). Role of RAD52 Epistasis Group Genes in Homologous Recombination and Double-Strand Break Repair. Microbiol. Mol. Biol. Rev. 66: 630-670 [Abstract] [Full Text]  
  • Tsai, Y.-L., Tseng, S.-F., Chang, S.-H., Lin, C.-C., Teng, S.-C. (2002). Involvement of Replicative Polymerases, Tel1p, Mec1p, Cdc13p, and the Ku Complex in Telomere-Telomere Recombination. Mol. Cell. Biol. 22: 5679-5687 [Abstract] [Full Text]  
  • Nakamura, T. M., Moser, B. A., Russell, P. (2002). Telomere Binding of Checkpoint Sensor and DNA Repair Proteins Contributes to Maintenance of Functional Fission Yeast Telomeres. Genetics 161: 1437-1452 [Abstract] [Full Text]  
  • Enomoto, S., Glowczewski, L., Berman, J. (2002). MEC3, MEC1, and DDC2 Are Essential Components of a Telomere Checkpoint Pathway Required for Cell Cycle Arrest during Senescence in Saccharomyces cerevisiae. Mol. Biol. Cell 13: 2626-2638 [Abstract] [Full Text]  
  • Craven, R. J., Greenwell, P. W., Dominska, M., Petes, T. D. (2002). Regulation of Genome Stability by TEL1 and MEC1, Yeast Homologs of the Mammalian ATM and ATR Genes. Genetics 161: 493-507 [Abstract] [Full Text]  
  • Myung, K., Kolodner, R. D. (2002). Inaugural Article: Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomycescerevisiae. Proc. Natl. Acad. Sci. USA 99: 4500-4507 [Abstract] [Full Text]  
  • Hathcock, K. S., Hemann, M. T., Opperman, K. K., Strong, M. A., Greider, C. W., Hodes, R. J. (2002). Haploinsufficiency of mTR results in defects in telomere elongation. Proc. Natl. Acad. Sci. USA 99: 3591-3596 [Abstract] [Full Text]  
  • Kishi, S., Lu, K. P. (2002). A Critical Role for Pin2/TRF1 in ATM-dependent Regulation. INHIBITION OF Pin2/TRF1 FUNCTION COMPLEMENTS TELOMERE SHORTENING, RADIOSENSITIVITY, AND THE G2/M CHECKPOINT DEFECT OF ATAXIA-TELANGIECTASIA CELLS. J. Biol. Chem. 277: 7420-7429 [Abstract] [Full Text]  
  • Schramke, V., Neecke, H., Brevet, V., Corda, Y., Lucchini, G., Longhese, M. P., Gilson, E., Geli, V. (2001). The set1{Delta} mutation unveils a novel signaling pathway relayed by the Rad53-dependent hyperphosphorylation of replication protein A that leads to transcriptional activation of repair genes. Genes Dev. 15: 1845-1858 [Abstract] [Full Text]  
  • Ray, A., Runge, K. W. (2001). Yeast telomerase appears to frequently copy the entire template in vivo. Nucleic Acids Res 29: 2382-2394 [Abstract] [Full Text]  
  • Craven, R. J., Petes, T. D. (2001). The Saccharomyces cerevisiae Suppressor of Choline Sensitivity (SCS2) Gene Is a Multicopy Suppressor of mec1 Telomeric Silencing Defects. Genetics 158: 145-154 [Abstract] [Full Text]  
  • Hande, M. P., Balajee, A. S., Tchirkov, A., Wynshaw-Boris, A., Lansdorp, P. M. (2001). Extra-chromosomal telomeric DNA in cells from Atm-/- mice and patients with ataxia-telangiectasia. Hum Mol Genet 10: 519-528 [Abstract] [Full Text]  
  • Gallego, M. E., White, C. I. (2001). RAD50 function is essential for telomere maintenance in Arabidopsis. Proc. Natl. Acad. Sci. USA 98: 1711-1716 [Abstract] [Full Text]  
  • Mallory, J. C., Petes, T. D. (2000). Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase. Proc. Natl. Acad. Sci. USA 10.1073/pnas.250475697v1 [Abstract] [Full Text]  
  • San-Segundo, P. A., Roeder, G. S. (2000). Role for the Silencing Protein Dot1 in Meiotic Checkpoint Control. Mol. Biol. Cell 11: 3601-3615 [Abstract] [Full Text]  
  • Longhese, M. P., Paciotti, V., Neecke, H., Lucchini, G. (2000). Checkpoint Proteins Influence Telomeric Silencing and Length Maintenance in Budding Yeast. Genetics 155: 1577-1591 [Abstract] [Full Text]  
  • Fritz, E., Friedl, A. A., Zwacka, R. M., Eckardt-Schupp, F., Meyn, M. S. (2000). The Yeast TEL1 Gene Partially Substitutes for Human ATM in Suppressing Hyperrecombination, Radiation-Induced Apoptosis and Telomere Shortening in A-T Cells. Mol. Biol. Cell 11: 2605-2616 [Abstract] [Full Text]  
  • Xia, J., Peng, Y., Mian, I. S., Lue, N. F. (2000). Identification of Functionally Important Domains in the N-Terminal Region of Telomerase Reverse Transcriptase. Mol. Cell. Biol. 20: 5196-5207 [Abstract] [Full Text]  
  • Forstemann, K., Hoss, M., Lingner, J. (2000). Telomerase-dependent repeat divergence at the 3' ends of yeast telomeres. Nucleic Acids Res 28: 2690-2694 [Abstract] [Full Text]  
  • Gasser, S. M. (2000). A Sense of the End. Science 288: 1377-1379 [Abstract] [Full Text]  
  • Ritchie, K. B., Petes, T. D. (2000). The Mre11p/Rad50p/Xrs2p Complex and the Tel1p Function in a Single Pathway for Telomere Maintenance in Yeast. Genetics 155: 475-479 [Abstract] [Full Text]  
  • Craven, R. J., Petes, T. D. (2000). Involvement of the Checkpoint Protein Mec1p in Silencing of Gene Expression at Telomeres in Saccharomyces cerevisiae. Mol. Cell. Biol. 20: 2378-2384 [Abstract] [Full Text]  
  • BLACKBURN, E.H., CHAN, S., CHANG, J., FULTON, T.B., KRAUSKOPF, A., MCEACHERN, M., PRESCOTT, J., ROY, J., SMITH, C., WANG, H. (2000). Molecular Manifestations and Molecular Determinants of Telomere Capping. Cold Spring Harb Symp Quant Biol 65: 253-264 [Abstract]  
  • DUBOIS, M.L., DIEDE, S.J., STELLWAGEN, A.E., GOTTSCHLING, D.E. (2000). All Things Must End: Telomere Dynamics in Yeast. Cold Spring Harb Symp Quant Biol 65: 281-296 [Abstract]  
  • WEINERT, T., LITTLE, E., SHANKS, L., ADMIRE, A., GARDNER, R., PUTNAM, C., MICHELSON, R., NYBERG, K., SUNDARESHAN, P. (2000). Details and Concerns Regarding the G2/M DNA Damage Checkpoint in Budding Yeast. Cold Spring Harb Symp Quant Biol 65: 433-442 [Abstract]  
  • Ray, A., Runge, K. W. (1999). Varying the number of telomere-bound proteins does not alter telomere length in tel1Delta cells. Proc. Natl. Acad. Sci. USA 96: 15044-15049 [Abstract] [Full Text]  
  • Myung, K., Kolodner, R. D. (2002). Inaugural Article: Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomycescerevisiae. Proc. Natl. Acad. Sci. USA 99: 4500-4507 [Abstract] [Full Text]  
  • Mallory, J. C., Petes, T. D. (2000). Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase. Proc. Natl. Acad. Sci. USA 97: 13749-13754 [Abstract] [Full Text]