Checkpoint Proteins Influence Telomeric Silencing and Length Maintenance in Budding Yeast

Corresponding author: Maria Pia Longhese, Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, P.zza della Scienza 2, 20126 Milano, Italy., mariapia.longhese{at}unimib.it (E-mail)

Communicating editor: A. G. HINNEBUSCH

A complex network of surveillance mechanisms, called checkpoints, interrupts cell cycle progression when damage to the genome is detected or when cells fail to complete DNA replication, thus ensuring genetic integrity. In budding yeast, components of the DNA damage checkpoint regulatory network include the RAD9, RAD17, RAD24, MEC3, DDC1, RAD53, and MEC1 genes that are proposed to be involved in different aspects of DNA metabolism. We provide evidence that some DNA damage checkpoint components play a role in maintaining telomere integrity. In fact, rad53 mutants specifically enhance repression of telomere-proximal transcription via the Sir-mediated pathway, suggesting that Rad53 might be required for proper chromatin structure at telomeres. Moreover, Rad53, Mec1, Ddc1, and Rad17 are necessary for telomere length maintenance, since mutations in all of these genes cause a decrease in telomere size. The telomeric shortening in rad53 and mec1 mutants is further enhanced in the absence of SIR genes, suggesting that Rad53/Mec1 and Sir proteins contribute to chromosome end protection by different pathways. The finding that telomere shortening, but not increased telomeric repression of gene expression in rad53 mutants, can be suppressed by increasing dNTP synthetic capacity in these strains suggests that transcriptional silencing and telomere integrity involve separable functions of Rad53.

This article has been cited by other articles:

				M. P. Longhese DNA damage response at functional and dysfunctional telomeres Genes & Dev., January 15, 2008; 22(2): 125 - 140. [Abstract] [Full Text] [PDF]

				F. Lottersberger, A. Panza, G. Lucchini, and M. P. Longhese Functional and Physical Interactions between Yeast 14-3-3 Proteins, Acetyltransferases, and Deacetylases in Response to DNA Replication Perturbations Mol. Cell. Biol., May 1, 2007; 27(9): 3266 - 3281. [Abstract] [Full Text] [PDF]

				J. Boerckel, D. Walker, and S. Ahmed The Caenorhabditis elegans Rad17 Homolog HPR-17 Is Required for Telomere Replication Genetics, May 1, 2007; 176(1): 703 - 709. [Abstract] [Full Text] [PDF]

				R. K. Pandita, G. G. Sharma, A. Laszlo, K. M. Hopkins, S. Davey, M. Chakhparonian, A. Gupta, R. J. Wellinger, J. Zhang, S. N. Powell, et al. Mammalian rad9 plays a role in telomere stability, s- and g2-phase-specific cell survival, and homologous recombinational repair. Mol. Cell. Biol., March 1, 2006; 26(5): 1850 - 1864. [Abstract] [Full Text] [PDF]

				J. Li and D. F. Stern DNA Damage Regulates Chk2 Association with Chromatin J. Biol. Chem., November 11, 2005; 280(45): 37948 - 37956. [Abstract] [Full Text] [PDF]

				J. A. Sharp, G. Rizki, and P. D. Kaufman Regulation of Histone Deposition Proteins Asf1/Hir1 by Multiple DNA Damage Checkpoint Kinases in Saccharomyces cerevisiae Genetics, November 1, 2005; 171(3): 885 - 899. [Abstract] [Full Text] [PDF]

				Y.-B. Chen, C.-P. Yang, R.-X. Li, R. Zeng, and J.-Q. Zhou Def1p Is Involved in Telomere Maintenance in Budding Yeast J. Biol. Chem., July 1, 2005; 280(26): 24784 - 24791. [Abstract] [Full Text] [PDF]

				M. Toussaint, I. Dionne, and R. J. Wellinger Limited TTP supply affects telomere length regulation in a telomerase-independent fashion Nucleic Acids Res., January 28, 2005; 33(2): 704 - 713. [Abstract] [Full Text] [PDF]

				M. Clerici, V. Baldo, D. Mantiero, F. Lottersberger, G. Lucchini, and M. P. Longhese A Tel1/MRX-Dependent Checkpoint Inhibits the Metaphase-to-Anaphase Transition after UV Irradiation in the Absence of Mec1 Mol. Cell. Biol., December 1, 2004; 24(23): 10126 - 10144. [Abstract] [Full Text] [PDF]

				F. d'Adda di Fagagna, S.-H. Teo, and S. P. Jackson Functional links between telomeres and proteins of the DNA-damage response Genes & Dev., August 1, 2004; 18(15): 1781 - 1799. [Abstract] [Full Text] [PDF]

				S. H. Askree, T. Yehuda, S. Smolikov, R. Gurevich, J. Hawk, C. Coker, A. Krauskopf, M. Kupiec, and M. J. McEachern From the Cover: A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length PNAS, June 8, 2004; 101(23): 8658 - 8663. [Abstract] [Full Text] [PDF]

				M. W. Van Dyke, L. D. Nelson, R. G. Weilbaecher, and D. V. Mehta Stm1p, a G4 Quadruplex and Purine Motif Triplex Nucleic Acid-binding Protein, Interacts with Ribosomes and Subtelomeric Y' DNA in Saccharomyces cerevisiae J. Biol. Chem., June 4, 2004; 279(23): 24323 - 24333. [Abstract] [Full Text] [PDF]

				D. Lydall Hiding at the ends of yeast chromosomes: telomeres, nucleases and checkpoint pathways J. Cell Sci., October 15, 2003; 116(20): 4057 - 4065. [Abstract] [Full Text] [PDF]

				V. Viscardi, E. Baroni, M. Romano, G. Lucchini, and M. P. Longhese Sudden Telomere Lengthening Triggers a Rad53-dependent Checkpoint in Saccharomyces cerevisiae Mol. Biol. Cell, August 1, 2003; 14(8): 3126 - 3143. [Abstract] [Full Text] [PDF]

				M. A. Jedrusik and E. Schulze Telomeric Position Effect Variegation in Saccharomyces cerevisiae by Caenorhabditis elegans Linker Histones Suggests a Mechanistic Connection between Germ Line and Telomeric Silencing Mol. Cell. Biol., May 15, 2003; 23(10): 3681 - 3691. [Abstract] [Full Text] [PDF]

				M. Dahlen, P. Sunnerhagen, and T. S.-F. Wang Replication Proteins Influence the Maintenance of Telomere Length and Telomerase Protein Stability Mol. Cell. Biol., May 1, 2003; 23(9): 3031 - 3042. [Abstract] [Full Text] [PDF]

				H. Qi, T.-K. Li, D. Kuo, A. Nur-E-Kamal, and L. F. Liu Inactivation of Cdc13p Triggers MEC1-dependent Apoptotic Signals in Yeast J. Biol. Chem., April 18, 2003; 278(17): 15136 - 15141. [Abstract] [Full Text] [PDF]

				T. M. Nakamura, B. A. Moser, and P. Russell Telomere Binding of Checkpoint Sensor and DNA Repair Proteins Contributes to Maintenance of Functional Fission Yeast Telomeres Genetics, August 1, 2002; 161(4): 1437 - 1452. [Abstract] [Full Text] [PDF]

				K. Myung and R. D. Kolodner Inaugural Article: Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomycescerevisiae PNAS, April 2, 2002; 99(7): 4500 - 4507. [Abstract] [Full Text] [PDF]

				Y. Huang Transcriptional silencing in Saccharomyces cerevisiae and Schizosaccharomyces pombe Nucleic Acids Res., April 1, 2002; 30(7): 1465 - 1482. [Abstract] [Full Text] [PDF]

				V. Paciotti, M. Clerici, M. Scotti, G. Lucchini, and M. P. Longhese Characterization of mec1 Kinase-Deficient Mutants and of New Hypomorphic mec1 Alleles Impairing Subsets of the DNA Damage Response Pathway Mol. Cell. Biol., June 15, 2001; 21(12): 3913 - 3925. [Abstract] [Full Text]

				F. Hu, A. A. Alcasabas, and S. J. Elledge Asf1 links Rad53 to control of chromatin assembly Genes & Dev., May 1, 2001; 15(9): 1061 - 1066. [Abstract] [Full Text]

				R. J. Craven and T. D. Petes The Saccharomyces cerevisiae Suppressor of Choline Sensitivity (SCS2) Gene Is a Multicopy Suppressor of mec1 Telomeric Silencing Defects Genetics, May 1, 2001; 158(1): 145 - 154. [Abstract] [Full Text]

				K. Myung and R. D. Kolodner Inaugural Article: Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomycescerevisiae PNAS, April 2, 2002; 99(7): 4500 - 4507. [Abstract] [Full Text] [PDF]