An alternative pathway for yeast telomere maintenance rescues est1− senescence

Lundblad, Victoria; Blackburn, Elizabeth H.

doi:10.1016/0092-8674(93)90234-h

Cited by 888 publications

(1,019 citation statements)

References 44 publications

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“…When telomerase-deficient cells senesce, survivors emerge in which telomeres are added by recombination 5 . When only the Rad51-dependent (requires Rad52, Rad54, Rdh54, Rad55, Rad57) recombination pathway is active, telomeres are characterized by short TG 1-3 repeats (type I telomeres), whereas when only the Rad59-dependent (requires Rad52, Rdh54, Rad50, Mre11, Xrs2) recombination pathway is active, telomeres are characterized by long TG 1-3 repeats (type II telomeres; refs.…”

Section: E T T E R Smentioning

confidence: 99%

“…Checkpoint defects 3 allow broken DNAs to replicate, which allows Figure 3 Model for the formation of GCRs in telomerase-deficient cells. In the absence of telomerase, the telomeres added by recombination 5,6 do not prevent the joining of telomeres to broken DNAs at low rates. In the absence of either of the Rad51 or Rad59 recombination pathways or Tel1, there are either increased levels of broken chromosomes that escape repair, decreased telomere protection, or both such that increased GCRs occur.…”

Section: E T T E R Smentioning

confidence: 99%

“…Proteins such as Pif1 help regulate telomere length 3 and prevent telomerase from adding telomeres to broken DNAs 3,4 . In telomerase-deficient S. cerevisiae cells telomeres are maintained by recombination 5,6 . Most mammalian cells lack telomerase 7 and have a limited lifespan.…”

mentioning

confidence: 99%

“…We did not examine rad52 mutations because they are lethal in combination with telomerase defects 5 . The GCR rates in rad51 tlc1, rad55 tlc1, rad54 tlc1, rad59 tlc1 and rdh54 tlc1 double mutants were not different (P > 0.10).…”

mentioning

confidence: 99%

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Recombination and the Tel1 and Mec1 checkpoints differentially effect genome rearrangements driven by telomere dysfunction in yeast

Pennaneach

Kolodner

2004

Nat Genet

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In telomerase-deficient Saccharomyces cerevisiae, telomeres are maintained by recombination. Here we used a S. cerevisiae assay for characterizing gross chromosomal rearrangements (GCRs) to analyze genome instability in post-senescent telomerase-deficient cells. Telomerase-deficient tlc1 and est2 mutants did not have increased GCR rates, but their telomeres could be joined to other DNAs resulting in chromosome fusions. Inactivation of Tel1 or either the Rad51 or Rad59 recombination pathways in telomerase-deficient cells increased the GCR rate, even though telomeres were maintained. The GCRs were translocations and chromosome fusions formed by nonhomologous end joining. We observed chromosome fusions only in mutant strains expressing Rad51 and Rad55 or when Tel1 was inactivated. In contrast, inactivation of Mec1 resulted in more inversion translocations such as the isochromosomes seen in human tumors. These inversion translocations seemed to be formed by recombination after replication of broken chromosomes.Telomeres function in replication and maintenance of chromosome ends, to prevent DNA ends from being inappropriately joined to each other and to prevent chromosome ends from activating checkpoints 1,2 . Telomeres are maintained by telomerase, which consists of the Est2 catalytic subunit, the Tlc1 RNA and other subunits 2 .Telomere maintenance also requires other proteins. These include the Tel1 protein kinase that functions in telomere protection and length regulation and proteins such as Cdc13 and Ku that target telomerase to telomeres and protect telomeres from degradation 2 . Proteins such as Pif1 help regulate telomere length 3 and prevent telomerase from adding telomeres to broken DNAs 3,4 . In telomerase-deficient S. cerevisiae cells telomeres are maintained by recombination 5,6 . Most mammalian cells lack telomerase 7 and have a limited lifespan. Immortalization and cancer progression require increased telomere maintenance capacity, either through upregulation of telomerase activity 7 or through the alternative lengthening of telomere pathway 8 .Recombination and the Tel1 and Mec1 checkpoints differentially effect genome rearrangements driven by telomere dysfunction in yeast L E T T E R S 612VOLUME 36 | NUMBER 6 | JUNE 2004 NATURE GENETICS RDKY5233 is a tlc1∆ type II strain. Additional relevant GCR rates include the tlc1∆ type I strain, RDKY5232 (3.1 × 10 -10 (0.9)); lig4∆ strain, RDKY3641 (1.6 × 10 -9 (9); ref. 10); tel1∆ lig4∆ strain, RDKY5238 (4.2 × 10 -9 (12)); and tel1∆ lig4∆ est2∆ strain, RDKY5240 (3.5 × 10 -9 (10)). ND, not determined.

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Section: E T T E R Smentioning

confidence: 99%

Section: E T T E R Smentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Recombination and the Tel1 and Mec1 checkpoints differentially effect genome rearrangements driven by telomere dysfunction in yeast

Pennaneach

Kolodner

2004

Nat Genet

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“…The most probable function of repetitive subtelomere sequences is to prevent telomere shortening, such as in the case of telomerase activity loss (Lundblad and Blackburn 1993). The formation of telomere loops (T-loops) is one of the broadly known chromosomal end features that protects against degradation of telomere ends.…”

Section: Sequence Characteristics Of Tatr7 and Tatr10smentioning

confidence: 99%

Toward closing rice telomere gaps: mapping and sequence characterization of rice subtelomere regions

Yang

Chang

et al. 2005

Theor Appl Genet

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Maintenance of telomeres in SV40-transformed pre-immortal and immortal human fibroblasts

et al. 1996

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Shortening of telomeres has been hypothesized to contribute to cellular senescence and may play a role in carcinogenesis of human cells. Furthermore, activation of telomerase has frequently been demonstrated in tumor-derived and in vitro immortalized cells. In this study, we have assessed these phenomena during the life span of simian virus 40 (SV40)-transformed preimmortal and immortal human fibroblasts. We observed progressive reduction in telomere length in preimmortal transformed cells with extended proliferative capacity, with the most dramatic shortening at late passage. Telomere lengths became stabilized (or increased) in immortal fibroblasts accompanied, in one case, by the activation of telomerase. However, an independent immortal cell line that displayed stable telomeres did not have detectable telomerase activity. Furthermore, we found significant telomerase activity in two preimmortal derivatives. Our results provide further evidence for maintenance of telomeres in immortalized human fibroblasts, but they suggest a lack of causal relationship between telomerase activation and immortalization.

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An alternative pathway for yeast telomere maintenance rescues est1− senescence

Cited by 888 publications

References 44 publications

Recombination and the Tel1 and Mec1 checkpoints differentially effect genome rearrangements driven by telomere dysfunction in yeast

Recombination and the Tel1 and Mec1 checkpoints differentially effect genome rearrangements driven by telomere dysfunction in yeast

Toward closing rice telomere gaps: mapping and sequence characterization of rice subtelomere regions

Maintenance of telomeres in SV40-transformed pre-immortal and immortal human fibroblasts

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