A Mutation in the <i>STN1</i> Gene Triggers an Alternative Lengthening of Telomere-Like Runaway Recombinational Telomere Elongation and Rapid Deletion in Yeast

Iyer, Shilpa; Chadha, Ashley D.; McEachern, Michael J.

doi:10.1128/mcb.25.18.8064-8073.2005

Cited by 33 publications

(75 citation statements)

References 73 publications

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“…7D). This somewhat rapid shortening of stn1-13 telomeres is reminiscent of a telomere rapid deletion (TRD) phenotype described for an stn1 mutant of Kluyveromyces lactis (34). Intriguingly, we observed that stn1-13 could trigger the ILT pathway.…”

Section: Fig 8 Kinetics Of Telomeric Recombination In Rad52mentioning

confidence: 62%

Telomerase- and Rad52-Independent Immortalization of Budding Yeast by an Inherited-Long-Telomere Pathway of Telomeric Repeat Amplification

Grandin

Charbonneau

2009

Molecular and Cellular Biology

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In the absence of telomerase, telomeres erode, provoking accumulation of DNA damage and death by senescence. Rare survivors arise, however, due to Rad52-based amplification of telomeric sequences by homologous recombination. The present study reveals that in budding yeast cells, postsenescence survival relying on amplification of the TG 1-3 telomeric repeats can take place in the absence of Rad52 when overelongated telomeres are present during senescence (hence its designation ILT, for inherited-long-telomere, pathway). By growth competition, the Rad52-independent pathway was almost as efficient as the Rad51-and Rad52-dependent pathway that predominates in telomerase-negative cells. The ILT pathway could also be triggered by increased telomerase accessibility before telomerase removal, combined with loss of telomere protection, indicating that prior accumulation of recombination proteins was not required. The ILT pathway was dependent on Rad50 and Mre11 but not on the Rad51 recombinase and Rad59, thus making it distinct from both the type II (budding yeast ALT [alternative lengthening of telomeres]) and type I pathways amplifying the TG 1-3 repeats and subtelomeric sequences, respectively. The ILT pathway also required the Rad1 endonuclease and Elg1, a replication factor C (RFC)-like complex subunit, but not Rad24 or Ctf18 (two subunits of two other RFC-like complexes), the Dnl4 ligase, Yku70, or Nej1. Possible mechanisms for this Rad52-independent pathway of telomeric repeat amplification are discussed. The effects of inherited long telomeres on Rad52-dependent recombination are also reported.

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Section: Fig 8 Kinetics Of Telomeric Recombination In Rad52mentioning

confidence: 62%

Telomerase- and Rad52-Independent Immortalization of Budding Yeast by an Inherited-Long-Telomere Pathway of Telomeric Repeat Amplification

Grandin

Charbonneau

2009

Molecular and Cellular Biology

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“…Such internal single-strand telomere sequences have been detected in both ''type II'' telomerase-deficient strains that survive senescence by employing a RAD52-and RAD50-dependent recombination pathway to maintain telomere function (Larrivee and Wellinger 2006). They have also been detected to some extent in the K. lactis stn1-M1 mutant strain (Iyer et al 2005). The type II survivor cells amplify their TG 1-3 telomere repeat sequences such that their terminal restriction fragments typically migrate on a Southern blot as a mix of distinct fragments.…”

Section: Nonoverlapping Regions Of Stn1p Interact With Ten1pmentioning

confidence: 73%

“…The type II survivor cells amplify their TG 1-3 telomere repeat sequences such that their terminal restriction fragments typically migrate on a Southern blot as a mix of distinct fragments. In contrast, in the stn1-186t, stn1-281t, and in the K. lactis stn1-M1 strains (Iyer et al 2005), telomerase is active and, in the case of the stn1-186t cells, sufficient for telomeres to appear as a heterogeneous smear. Thus, the loss of telomere integrity observed in the stn1-t strains has characteristics that distinguish it in comparison with other mutant strains that show end-protection defects.…”

Section: Nonoverlapping Regions Of Stn1p Interact With Ten1pmentioning

confidence: 93%

“…stn1-281t, but not stn1-186t, requires homologous recombination for viability: Elongated telomere tracts are typically generated through the activity of telomerase, although homologous recombination can in some cases amplify telomere sequences. Since it has been demonstrated that a mutant allele of the STN1 homolog in Kluyveromyces lactis requires homologous recombination for viability (Iyer et al 2005), we first used tetrad analysis to test whether RAD52 is essential for growth in either stn1-186t or stn1-281t strains. Interestingly, stn1-281t rad52-D haploids were never recovered from heterozygous diploids (23 tetrads dissected), indicating that RAD52 is essential for viability of the stn1-281t strain.…”

Section: Nonoverlapping Regions Of Stn1p Interact With Ten1pmentioning

confidence: 99%

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The Role of Stn1p inSaccharomyces cerevisiaeTelomere Capping Can Be Separated From Its Interaction With Cdc13p

2007

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The function of telomeres is twofold: to facilitate complete chromosome replication and to protect chromosome ends against fusions and illegitimate recombination. In the budding yeast Saccharomyces cerevisiae, interactions among Cdc13p, Stn1p, and Ten1p are thought to be critical for promoting these processes. We have identified distinct Stn1p domains that mediate interaction with either Ten1p or Cdc13p, allowing analysis of whether the interaction between Cdc13p and Stn1p is indeed essential for telomere capping or length regulation. Consistent with the model that the Stn1p essential function is to promote telomere end protection through Cdc13p, stn1 alleles that truncate the C-terminal 123 residues fail to interact with Cdc13p and do not support viability when expressed at endogenous levels. Remarkably, more extensive deletions that remove an additional 185 C-terminal residues from Stn1p now allow cell growth at endogenous expression levels. The viability of these stn1-t alleles improves with increasing expression level, indicating that increased stn1-t dosage can compensate for the loss of Cdc13p-Stn1p interaction. However, telomere length is misregulated at all expression levels. Thus, an amino-terminal region of Stn1p is sufficient for its essential function, while a central region of Stn1p either negatively regulates the STN1 essential function or destabilizes the mutant Stn1 protein.

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“…For instance, in S. cerevisiae, a cdc13-1 yku70 mutation at the semipermissive temperature caused type II survivors to form after a period of senescence-like growth without appreciably shortened telomeres (23). In K. lactis, a mutation in the telomereassociated protein Stn1 (stn1-M1) led to RTE that produced highly elongated and unstable telomeres and other features that distinguished it from the RTE of telomerase deletion survivors (33). The stn1-M1 cells had a chronic moderate growth defect but failed to display the large changes in growth rate that characterize senescence and survivor formation.…”

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confidence: 99%

Mutant Telomeric Repeats in Yeast Can Disrupt the Negative Regulation of Recombination-Mediated Telomere Maintenance and Create an Alternative Lengthening of Telomeres-Like Phenotype

Bechard

Bütüner

Peterson

et al. 2009

Molecular and Cellular Biology

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Some human cancers maintain telomeres using alternative lengthening of telomeres (ALT), a process thought to be due to recombination. In Kluyveromyces lactis mutants lacking telomerase, recombinational telomere elongation (RTE) is induced at short telomeres but is suppressed once telomeres are moderately elongated by RTE. Recent work has shown that certain telomere capping defects can trigger a different type of RTE that results in much more extensive telomere elongation that is reminiscent of human ALT cells. In this study, we generated telomeres composed of either of two types of mutant telomeric repeats, Acc and SnaB, that each alter the binding site for the telomeric protein Rap1. We show here that arrays of both types of mutant repeats present basally on a telomere were defective in negatively regulating telomere length in the presence of telomerase. Similarly, when each type of mutant repeat was spread to all chromosome ends in cells lacking telomerase, they led to the formation of telomeres produced by RTE that were much longer than those seen in cells with only wild-type telomeric repeats. The Acc repeats produced the more severe defect in both types of telomere maintenance, consistent with their more severe Rap1 binding defect. Curiously, although telomerase deletion mutants with telomeres composed of Acc repeats invariably showed extreme telomere elongation, they often also initially showed persistent very short telomeres with few or no Acc repeats. We suggest that these result from futile cycles of recombinational elongation and truncation of the Acc repeats from the telomeres. The presence of extensive 3 overhangs at mutant telomeres suggests that Rap1 may normally be involved in controlling 5 end degradation.

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A Mutation in the STN1 Gene Triggers an Alternative Lengthening of Telomere-Like Runaway Recombinational Telomere Elongation and Rapid Deletion in Yeast

Cited by 33 publications

References 73 publications

Telomerase- and Rad52-Independent Immortalization of Budding Yeast by an Inherited-Long-Telomere Pathway of Telomeric Repeat Amplification

Telomerase- and Rad52-Independent Immortalization of Budding Yeast by an Inherited-Long-Telomere Pathway of Telomeric Repeat Amplification

The Role of Stn1p inSaccharomyces cerevisiaeTelomere Capping Can Be Separated From Its Interaction With Cdc13p

Mutant Telomeric Repeats in Yeast Can Disrupt the Negative Regulation of Recombination-Mediated Telomere Maintenance and Create an Alternative Lengthening of Telomeres-Like Phenotype

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