Genetics, Vol. 152, 143-152, May 1999, Copyright © 1999

RAD50 and RAD51 Define Two Pathways That Collaborate to Maintain Telomeres in the Absence of Telomerase

Siyuan Lea,b, J. Kent Moorec, James E. Haberc, and Carol W. Greidera,b
a Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,
b Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724
c Rosenstiel Center MS029, Brandeis University, Waltham, Massachusetts 02454-9110

Corresponding author: Carol W. Greider, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 617 Hunterian Bldg., 725 N. Wolfe St., Baltimore, MD 21205., cgreider{at}bs.jhmi.edu (E-mail)

Communicating editor: L. S. SYMINGTON

Telomere length is maintained by the de novo addition of telomere repeats by telomerase, yet recombination can elongate telomeres in the absence of telomerase. When the yeast telomerase RNA component, TLC1, is deleted, telomeres shorten and most cells die. However, gene conversion mediated by the RAD52 pathway allows telomere lengthening in rare survivor cells. To further investigate the role of recombination in telomere maintenance, we assayed telomere length and the ability to generate survivors in several isogenic DNA recombination mutants, including rad50, rad51, rad52, rad54, rad57, xrs2, and mre11. The rad51, rad52, rad54, and rad57 mutations increased the rate of cell death in the absence of TLC1. In contrast, although the rad50, xrs2, and mre11 strains initially had short telomeres, double mutants with tlc1 did not affect the rate of cell death, and survivors were generated at later times than tlc1 alone. While none of the double mutants of recombination genes and tlc1 (except rad52 tlc1) blocked the ability to generate survivors, a rad50 rad51 tlc1 triple mutant did not allow the generation of survivors. Thus RAD50 and RAD51 define two separate pathways that collaborate to allow cells to survive in the absence of telomerase.





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GeneticsHome page
H. L. Klein
Mutations in Recombinational Repair and in Checkpoint Control Genes Suppress the Lethal Combination of srs2{{Delta}} With Other DNA Repair Genes in Saccharomyces cerevisiae
Genetics, February 1, 2001; 157(2): 557 - 565.
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Mol. Cell. Biol.Home page
L. E. Kang and L. S. Symington
Aberrant Double-Strand Break Repair in rad51 Mutants of Saccharomyces cerevisiae
Mol. Cell. Biol., December 15, 2000; 20(24): 9162 - 9172.
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Nucleic Acids ResHome page
L. Tomaska, J. Nosek, A. M. Makhov, A. Pastorakova, and J. D. Griffith
Extragenomic double-stranded DNA circles in yeast with linear mitochondrial genomes: potential involvement in telomere maintenance
Nucleic Acids Res., November 15, 2000; 28(22): 4479 - 4487.
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Proc. Natl. Acad. Sci. USAHome page
S. T. Merino, W. J. Cummings, S. N. Acharya, and M. E. Zolan
Replication-dependent early meiotic requirement for Spo11 and Rad50
PNAS, September 5, 2000; (2000) 190346097.
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Nucleic Acids ResHome page
X. Pan and D. R. F. Leach
The roles of mutS, sbcCD and recA in the propagation of TGG repeats in Escherichia coli
Nucleic Acids Res., August 15, 2000; 28(16): 3178 - 3184.
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Nucleic Acids ResHome page
N. A. Lanson Jr, D. B. Egeland, B. A. Royals, and W. C. Claycomb
The MRE11-NBS1-RAD50 pathway is perturbed in SV40 large T antigen-immortalized AT-1, AT-2 and HL-1 cardiomyocytes
Nucleic Acids Res., August 1, 2000; 28(15): 2882 - 2892.
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Mol. Cell. Biol.Home page
J. Xia, Y. Peng, I. S. Mian, and N. F. Lue
Identification of Functionally Important Domains in the N-Terminal Region of Telomerase Reverse Transcriptase
Mol. Cell. Biol., July 15, 2000; 20(14): 5196 - 5207.
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Mol. Cell. Biol.Home page
V. I. Bashkirov, J. S. King, E. V. Bashkirova, J. Schmuckli-Maurer, and W.-D. Heyer
DNA Repair Protein Rad55 Is a Terminal Substrate of the DNA Damage Checkpoints
Mol. Cell. Biol., June 15, 2000; 20(12): 4393 - 4404.
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Proc. Natl. Acad. Sci. USAHome page
C. L. Limoli, E. Giedzinski, W. F. Morgan, and J. E. Cleaver
Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair
PNAS, June 14, 2000; (2000) 130182897.
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Mol. Cell. Biol.Home page
H. Niida, Y. Shinkai, M. P. Hande, T. Matsumoto, S. Takehara, M. Tachibana, M. Oshimura, P. M. Lansdorp, and Y. Furuichi
Telomere Maintenance in Telomerase-Deficient Mouse Embryonic Stem Cells: Characterization of an Amplified Telomeric DNA
Mol. Cell. Biol., June 1, 2000; 20(11): 4115 - 4127.
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Cancer Res.Home page
D. B. Lombard and L. Guarente
Nijmegen Breakage Syndrome Disease Protein and MRE11 at PML Nuclear Bodies and Meiotic Telomeres
Cancer Res., May 1, 2000; 60(9): 2331 - 2334.
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GeneticsHome page
K. B. Ritchie and T. D. Petes
The Mre11p/Rad50p/Xrs2p Complex and the Tel1p Function in a Single Pathway for Telomere Maintenance in Yeast
Genetics, May 1, 2000; 155(1): 475 - 479.
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GeneticsHome page
B. Fellerhoff, F. Eckardt-Schupp, and A. A. Friedl
Subtelomeric Repeat Amplification Is Associated With Growth at Elevated Temperature in yku70 Mutants of Saccharomyces cerevisiae
Genetics, March 1, 2000; 154(3): 1039 - 1051.
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J. Cell Sci.Home page
J. Grobelny, A. Godwin, and D Broccoli
ALT-associated PML bodies are present in viable cells and are enriched in cells in the G(2)/M phase of the cell cycle
J. Cell Sci., January 12, 2000; 113(24): 4577 - 4585.
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Cold Spring Harb Symp Quant BiolHome page
E.H. BLACKBURN, S. CHAN, J. CHANG, T.B. FULTON, A. KRAUSKOPF, M. MCEACHERN, J. PRESCOTT, J. ROY, C. SMITH, and H. WANG
Molecular Manifestations and Molecular Determinants of Telomere Capping
Cold Spring Harb Symp Quant Biol, January 1, 2000; 65(0): 253 - 264.
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Cold Spring Harb Symp Quant BiolHome page
T. DE LANGE and J.H.J. PETRINI
A New Connection at Human Telomeres: Association of the Mre11 Complex with TRF2
Cold Spring Harb Symp Quant Biol, January 1, 2000; 65(0): 265 - 274.
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Cold Spring Harb Symp Quant BiolHome page
M.L. DUBOIS, S.J. DIEDE, A.E. STELLWAGEN, and D.E. GOTTSCHLING
All Things Must End: Telomere Dynamics in Yeast
Cold Spring Harb Symp Quant Biol, January 1, 2000; 65(0): 281 - 296.
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Mol. Cell. Biol.Home page
S.-C. Teng and V. A. Zakian
Telomere-Telomere Recombination Is an Efficient Bypass Pathway for Telomere Maintenance in Saccharomyces cerevisiae
Mol. Cell. Biol., December 1, 1999; 19(12): 8083 - 8093.
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J. Biol. Chem.Home page
G. Wu, W.-H. Lee, and P.-L. Chen
NBS1 and TRF1 Colocalize at Promyelocytic Leukemia Bodies during Late S/G2 Phases in Immortalized Telomerase-negative Cells. IMPLICATION OF NBS1 IN ALTERNATIVE LENGTHENING OF TELOMERES
J. Biol. Chem., September 22, 2000; 275(39): 30618 - 30622.
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J. Biol. Chem.Home page
L. P. Ford, Y. Zou, K. Pongracz, S. M. Gryaznov, J. W. Shay, and W. E. Wright
Telomerase Can Inhibit the Recombination-based Pathway of Telomere Maintenance in Human Cells
J. Biol. Chem., August 17, 2001; 276(34): 32198 - 32203.
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Proc. Natl. Acad. Sci. USAHome page
H. Cohen and D. A. Sinclair
Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase
PNAS, March 13, 2001; 98(6): 3174 - 3179.
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Proc. Natl. Acad. Sci. USAHome page
T. T. Paull and M. Gellert
A mechanistic basis for Mre11-directed DNA joining at microhomologies
PNAS, June 6, 2000; 97(12): 6409 - 6414.
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Proc. Natl. Acad. Sci. USAHome page
C. L. Limoli, E. Giedzinski, W. F. Morgan, and J. E. Cleaver
Inaugural Article: Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair
PNAS, July 5, 2000; 97(14): 7939 - 7946.
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Proc. Natl. Acad. Sci. USAHome page
S. T. Merino, W. J. Cummings, S. N. Acharya, and M. E. Zolan
Replication-dependent early meiotic requirement for Spo11 and Rad50
PNAS, September 12, 2000; 97(19): 10477 - 10482.
[Abstract] [Full Text] [PDF]