Abstract
Recombination-dependent maintenance of telomeres, first discovered in budding yeast, has revealed an alternative pathway for telomere maintenance that does not require the enzyme telomerase. Experiments conducted in two budding yeasts, S. cerevisiae and K. lactis, have shown recombination can replenish terminal G-rich telomeric tracts that would otherwise shorten in the absence of telomerase, as well as disperse and amplify sub-telomeric repeat elements. Investigation of the genetic requirements for this process have revealed that at least two different recombination pathways, defined by RAD50 and RAD51, can promote telomere maintenance. Although critically short telomeres are very recombinogenic, recombination among telomeres that have only partially shortened in the absence of telomerase can also contribute to telomerase-independent survival. These observations provide new insights into the mechanism(s) by which recombination can restore telomere function in yeast, and suggest future experiments for the investigation of potentially similar pathways in human cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Baird DM, Coleman J, Rosser ZH, Royle NJ . 2000 Am. J. Hum. Genet. 66: 235–250
Baird DM, Jeffreys AJ, Royle NJ . 1995 EMBO J. 14: 5433–5443
Bernards A, Michels PA, Lincke CR, Borst P . 1983 Nature 303: 592–597
Biessmann H, Mason JM . 1997 Chromosoma 106: 63–69
Blackburn EH . 2001 Cell 106: 661–673
Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu C-P, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE . 1998 Science 279: 349–352
Bosco G, Haber JE . 1998 Genetics 150: 1037–1047
Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR . 1997 Nat. Med. 3: 1271–1274
Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR . 1995 EMBO J. 14: 4240–4248
Bucholc M, Park Y, Lustig AJ . 2001 Mol. Cell. Biol. 21: 6559–6573
Cerone MA, Londono-Vallejo JA, Bacchetti S . 2001 Hum. Mol. Genet. 10: 1945–1952
Chan CS, Tye BK . 1983 J. Mol. Biol. 168: 505–523
Chen Q, Ijpma A, Greider CW . 2001 Mol. Cell. Biol. 21: 1819–1827
Cohen H, Sinclair DA . 2001 Proc. Natl. Acad. Sci. USA 98: 3174–3179
Dunham MA, Neumann AA, Fasching CL, Reddel RR . 2000 Nat. Genet. 26: 447–450
Dunn B, Szauter P, Pardue ML, Szostak JW . 1984 Cell 39: 191–201
Ford LP, Zou Y, Pongracz K, Gryaznov SM, Shay JW, Wright WE . 2001 J. Biol. Chem. 276: 32198–32203
Formosa T, Alberts BM . 1986 J. Biol. Chem. 261: 6107–6118
Greider CW . 1996 Annu. Rev. Biochem. 65: 337–365
Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T . 1999 Cell 97: 503–514
Grobelny JV, Kulp-McEliece M, Broccoli D . 2001 Hum. Mol. Genet. 10: 1953–1961
Hackett JA, Feldser DM, Greider CW . 2001 Cell 106: 275–286
Horowitz H, Haber JE . 1985 Mol. Cell. Biol. 5: 2369–2380
Huang P, Pryde FE, Lester D, Maddison RL, Borts RH, Hickson ID, Louis EJ . 2001 Curr. Biol. 11: 125–129
Hughes TR, Evans SK, Weilbaecher RG, Lundblad V . 2000 Curr. Biol. 10: 809–812
Johnson FB, Marciniak RA, McVey M, Stewart SA, Hahn WC, Guarente L . 2001 EMBO J. 20: 905–913
Kass-Eisler A, Greider CW . 2000 Trends Biochem. Sci. 25: 200–204
Kramer KM, Haber JE . 1993 Genes Dev. 7: 2345–2356
Kraus E, Leung WY, Haber JE . 2001 Proc. Natl. Acad. Sci. USA 98: 8255–8262
Le S, Moore JK, Haber JE, Greider CW . 1999 Genetics 152: 143–152
Lendvay TS, Morris DK, Sah J, Balasubramanian B, Lundblad V . 1996 Genetics 144: 1399–1412
Li B, Lustig AJ . 1996 Genes Dev. 10: 1310–1326
Luder A, Mosig G . 1982 Proc. Natl. Acad. Sci. USA 79: 1101–1105
Lundblad V . 2000 Mutat. Res. 451: 227–240
Lundblad V, Blackburn EH . 1993 Cell 73: 347–360
Lundblad V, Szostak JW . 1989 Cell 57: 633–643
Malkova A, Signon L, Schaefer CB, Naylor ML, Theis JF, Newlon CS, Haber JE . 2001 Genes Dev. 15: 1055–1060
McEachern MJ, Blackburn EH . 1995 Nature 376: 403–409
McEachern MJ, Blackburn EH . 1996 Genes Dev. 10: 1822–1834
McEachern MJ, Iyer S . 2001 Mol. Cell. 7: 695–704
McEachern MJ, Krauskopf A, Blackburn EH . 2000 Annu. Rev. Genet. 34: 331–358
Meltzer PS, Guan XY, Trent JM . 1993 Nature Genet. 4: 252–255
Morin GB . 1989 Cell 59: 521–529
Morris DK, Lundblad V . 1997 Curr. Biol. 7: 969–976
Munoz-Jordan JL, Cross GA, de Lange T, Griffith JD . 2001 EMBO J. 20: 579–588
Novick RP . 1998 Trends Biochem. Sci. 23: 434–438
Perrem K, Colgin LM, Neumann AA, Yeager TR, Reddel RR . 2001 Mol. Cell. Biol. 21: 3862–3875
Reddel RR, Bryan TM, Colgin LM, Perrem KT, Yeager TR . 2001 Radiat. Res. 155: 194–200
Rizki A, Lundblad V . 2001 Nature 411: 713–716
Sandell LL, Zakian VA . 1993 Cell 75: 729–739
Shay JW, Bacchetti S . 1997 Eur. J. Cancer 33: 787–791
Signon L, Malkova A, Naylor ML, Klein H, Haber JE . 2001 Mol. Cell. Biol. 21: 2048–2056
Singer MS, Gottschling DE . 1994 Science 266: 404–409
Teng CS, Chang J, McCowan B, Zakian AV . 2000 Mol. Cell. 6: 947–952
Teng SC, Zakian VA . 1999 Mol. Cell. Biol. 19: 8083–8093
Walmsley RW, Chan CS, Tye BK, Petes TD . 1984 Nature 310: 157–160
Wilkie AO, Higgs DR, Rack KA, Buckle VJ, Spurr NK, Fischel-Ghodsian N, Ceccherini I, Brown WR, Harris PC . 1991 Cell 64: 595–606
Yeager TR, Neumann AA, Englezou A, Huschtscha LI, Noble JR, Reddel RR . 1999 Cancer Res. 59: 4175–4179
Zhu XD, Kuster B, Mann M, Petrini JH, Lange T . 2000 Nat. Genet. 25: 347–352
Acknowledgements
I thank Jim Haber and Jenny Hackett for explaining the subtleties of the genetic requirements of BIR to me, Sara Evans for excellent editorial assistance and figure preparation, and Lou Zumstein, Rachel Cervantes and Erin Pennock for critical reading of the manuscript. Work in the author’s laboratory is supported by grants from the NIH and the Ellison Medical Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lundblad, V. Telomere maintenance without telomerase. Oncogene 21, 522–531 (2002). https://doi.org/10.1038/sj.onc.1205079
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205079
Keywords
This article is cited by
-
TelNet - a database for human and yeast genes involved in telomere maintenance
BMC Genetics (2018)
-
Telomerase activity is required for the telomere G-overhang structure in Trypanosoma brucei
Scientific Reports (2017)
-
Telomere recombination pathways: tales of several unhappy marriages
Current Genetics (2017)
-
Subtelomere organization in the genome of the microsporidian Encephalitozoon cuniculi: patterns of repeated sequences and physicochemical signatures
BMC Genomics (2016)
-
Holokinetic centromeres and efficient telomere healing enable rapid karyotype evolution
Chromosoma (2015)