Genetics, Vol. 161, 1437-1452, August 2002, Copyright © 2002

Telomere Binding of Checkpoint Sensor and DNA Repair Proteins Contributes to Maintenance of Functional Fission Yeast Telomeres

Toru M. Nakamuraa, Bettina A. Mosera, and Paul Russella
a Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037

Corresponding author: Toru M. Nakamura, MB3, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037., nakamut{at}scripps.edu (E-mail)

Communicating editor: G. SMITH

Telomeres, the ends of linear chromosomes, are DNA double-strand ends that do not trigger a cell cycle arrest and yet require checkpoint and DNA repair proteins for maintenance. Genetic and biochemical studies in the fission yeast Schizosaccharomyces pombe were undertaken to understand how checkpoint and DNA repair proteins contribute to telomere maintenance. On the basis of telomere lengths of mutant combinations of various checkpoint-related proteins (Rad1, Rad3, Rad9, Rad17, Rad26, Hus1, Crb2, Chk1, Cds1), Tel1, a telomere-binding protein (Taz1), and DNA repair proteins (Ku70, Rad32), we conclude that Rad3/Rad26 and Tel1/Rad32 represent two pathways required to maintain telomeres and prevent chromosome circularization. Rad1/Rad9/Hus1/Rad17 and Ku70 are two additional epistasis groups, which act in the Rad3/Rad26 pathway. However, Rad3/Rad26 must have additional target(s), as cells lacking Tel1/Rad32, Rad1/Rad9/Hus1/Rad17, and Ku70 groups did not circularize chromosomes. Cells lacking Rad3/Rad26 and Tel1/Rad32 senesced faster than a telomerase trt1{Delta} mutant, suggesting that these pathways may contribute to telomere protection. Deletion of taz1 did not suppress chromosome circularization in cells lacking Rad3/Rad26 and Tel1/Rad32, also suggesting that two pathways protect telomeres. Chromatin immunoprecipitation analyses found that Rad3, Rad1, Rad9, Hus1, Rad17, Rad32, and Ku70 associate with telomeres. Thus, checkpoint sensor and DNA repair proteins contribute to telomere maintenance and protection through their association with telomeres.




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
L. Subramanian, B. A. Moser, and T. M. Nakamura
Recombination-Based Telomere Maintenance Is Dependent on Tel1-MRN and Rap1 and Inhibited by Telomerase, Taz1, and Ku in Fission Yeast
Mol. Cell. Biol., March 1, 2008; 28(5): 1443 - 1455.
[Abstract] [Full Text] [PDF]

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

Home page
 Proc. Natl. Acad. Sci. USAHome page
V. Martin, L.-L. Du, S. Rozenzhak, and P. Russell
Protection of telomeres by a conserved Stn1 Ten1 complex
PNAS, August 28, 2007; 104(35): 14038 - 14043.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
T. Kibe, Y. Ono, K. Sato, and M. Ueno
Fission Yeast Taz1 and RPA Are Synergistically Required to Prevent Rapid Telomere Loss
Mol. Biol. Cell, June 1, 2007; 18(6): 2378 - 2387.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
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]

Home page
 GeneticsHome page
C. Noguchi and E. Noguchi
Sap1 Promotes the Association of the Replication Fork Protection Complex With Chromatin and Is Involved in the Replication Checkpoint in Schizosaccharomyces pombe
Genetics, February 1, 2007; 175(2): 553 - 566.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
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]

Home page
 Genes Dev.Home page
R. J. Michelson, S. Rosenstein, and T. Weinert
A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint
Genes & Dev., November 1, 2005; 19(21): 2546 - 2559.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
X. Bi, D. Srikanta, L. Fanti, S. Pimpinelli, R. Badugu, R. Kellum, and Y. S. Rong
Drosophila ATM and ATR checkpoint kinases control partially redundant pathways for telomere maintenance
PNAS, October 18, 2005; 102(42): 15167 - 15172.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Z. You, C. Chahwan, J. Bailis, T. Hunter, and P. Russell
ATM Activation and Its Recruitment to Damaged DNA Require Binding to the C Terminus of Nbs1
Mol. Cell. Biol., July 1, 2005; 25(13): 5363 - 5379.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. Tomita, T. Kibe, H.-Y. Kang, Y.-S. Seo, M. Uritani, T. Ushimaru, and M. Ueno
Fission Yeast Dna2 Is Required for Generation of the Telomeric Single-Strand Overhang
Mol. Cell. Biol., November 1, 2004; 24(21): 9557 - 9567.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. M. Hopkins, W. Auerbach, X. Y. Wang, M. P. Hande, H. Hang, D. J. Wolgemuth, A. L. Joyner, and H. B. Lieberman
Deletion of Mouse Rad9 Causes Abnormal Cellular Responses to DNA Damage, Genomic Instability, and Embryonic Lethality
Mol. Cell. Biol., August 15, 2004; 24(16): 7235 - 7248.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
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]

Home page
 Genes Dev.Home page
S. R. Oikemus, N. McGinnis, J. Queiroz-Machado, H. Tukachinsky, S. Takada, C. E. Sunkel, and M. H. Brodsky
Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect
Genes & Dev., August 1, 2004; 18(15): 1850 - 1861.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
T. M. Nakamura, L.-L. Du, C. Redon, and P. Russell
Histone H2A Phosphorylation Controls Crb2 Recruitment at DNA Breaks, Maintains Checkpoint Arrest, and Influences DNA Repair in Fission Yeast
Mol. Cell. Biol., July 15, 2004; 24(14): 6215 - 6230.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Nabetani, O. Yokoyama, and F. Ishikawa
Localization of hRad9, hHus1, hRad1, and hRad17 and Caffeine-sensitive DNA Replication at the Alternative Lengthening of Telomeres-associated Promyelocytic Leukemia Body
J. Biol. Chem., June 11, 2004; 279(24): 25849 - 25857.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
S. Coulon, P.-H. L. Gaillard, C. Chahwan, W. H. McDonald, J. R. Yates III, and P. Russell
Slx1-Slx4 Are Subunits of a Structure-specific Endonuclease That Maintains Ribosomal DNA in Fission Yeast
Mol. Biol. Cell, January 1, 2004; 15(1): 71 - 80.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Y. Ono, K. Tomita, A. Matsuura, T. Nakagawa, H. Masukata, M. Uritani, T. Ushimaru, and M. Ueno
A novel allele of fission yeast rad11 that causes defects in DNA repair and telomere length regulation
Nucleic Acids Res., December 15, 2003; 31(24): 7141 - 7149.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H. Zhao, K. Tanaka, E. Nogochi, C. Nogochi, and P. Russell
Replication Checkpoint Protein Mrc1 Is Regulated by Rad3 and Tel1 in Fission Yeast
Mol. Cell. Biol., November 15, 2003; 23(22): 8395 - 8403.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. A. Mieczkowski, J. O. Mieczkowska, M. Dominska, and T. D. Petes
Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisae
PNAS, September 16, 2003; 100(19): 10854 - 10859.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Ueno, T. Nakazaki, Y. Akamatsu, K. Watanabe, K. Tomita, H. D. Lindsay, H. Shinagawa, and H. Iwasaki
Molecular Characterization of the Schizosaccharomyces pombe nbs1+ Gene Involved in DNA Repair and Telomere Maintenance
Mol. Cell. Biol., September 15, 2003; 23(18): 6553 - 6563.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. Chahwan, T. M. Nakamura, S. Sivakumar, P. Russell, and N. Rhind
The Fission Yeast Rad32 (Mre11)-Rad50-Nbs1 Complex Is Required for the S-Phase DNA Damage Checkpoint
Mol. Cell. Biol., September 15, 2003; 23(18): 6564 - 6573.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. Tomita, A. Matsuura, T. Caspari, A. M. Carr, Y. Akamatsu, H. Iwasaki, K.-i. Mizuno, K. Ohta, M. Uritani, T. Ushimaru, et al.
Competition between the Rad50 Complex and the Ku Heterodimer Reveals a Role for Exo1 in Processing Double-Strand Breaks but Not Telomeres
Mol. Cell. Biol., August 1, 2003; 23(15): 5186 - 5197.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
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]