Telomerase-Independent Lengthening of Yeast Telomeres Occurs by an Abrupt Rad50p-Dependent, Rif-Inhibited Recombinational Process

Chang, Jaerak; McCowan, B.; Zakian, Virginia A.

doi:10.1016/s1097-2765(00)00092-7

Cited by 102 publications

(199 citation statements)

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“…2b,c). In a liquid culture assay, when cultures starting from freshly dissected spores were repeatedly diluted, telomere shortening and marked telomere lengthening from survivor formation could be observed in telomerase pathway-defective strains after several dilutions 44 . Similarly, cdc13-S249/255A cells displayed gradual telomere shortening, survivor formation and cellular senescence phenotypes, and these phenotypes were recovered in cdc13-S249/255D cells ( Supplementary Fig.…”

Section: Pp2a Dephosphorylates Cdc13 Serine 249 and 255mentioning

confidence: 99%

PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase

Shen

Hsu

et al. 2014

Nat Commun

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In yeast, the initiation of telomere replication at the late S phase involves in combined actions of kinases on Cdc13, the telomere binding protein. Cdc13 recruits telomerase to telomeres through its interaction with Est1, a component of telomerase. However, how cells terminate the function of telomerase at G2/M is still elusive. Here we show that the protein phosphatase 2A (PP2A) subunit Pph22 and the yeast Aurora kinase homologue Ipl1 coordinately inhibit telomerase at G2/M by dephosphorylating and phosphorylating the telomerase recruitment domain of Cdc13, respectively. While Pph22 removes Tel1/Mec1-mediated Cdc13 phosphorylation to reduce Cdc13-Est1 interaction, Ipl1-dependent Cdc13 phosphorylation elicits dissociation of Est1-TLC1, the template RNA component of telomerase. Failure of these regulations prevents telomerase from departing telomeres, causing perturbed telomere lengthening and prolonged M phase. Together our results demonstrate that differential and additive actions of PP2A and Aurora on Cdc13 limit telomerase action by removing active telomerase from telomeres at G2/M phase.

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Section: Pp2a Dephosphorylates Cdc13 Serine 249 and 255mentioning

confidence: 99%

PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase

Shen

Hsu

et al. 2014

Nat Commun

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“…Interestingly, however, rif1⌬ rad52⌬ double mutants also display a synergistic telomere elongation phenotype ( Fig. 6B; Teng et al 2000). These results raise the possibility that both rif1⌬ and pol12-216 mutations alter telomere structure in some rather unique way such as to favor the action of a RAD52-dependent telomere-shortening pathway.…”

Section: Discussionmentioning

confidence: 88%

Pol12, the B subunit of DNA polymerase α, functions in both telomere capping and length regulation

Grossi¹,

Puglisi²,

Dmitriev³

et al. 2004

Genes Dev.

129

173

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The regulation of telomerase action, and its coordination with conventional DNA replication and chromosome end "capping," are still poorly understood. Here we describe a genetic screen in yeast for mutants with relaxed telomere length regulation, and the identification of Pol12, the B subunit of the DNA polymerase ␣ (Pol1)-primase complex, as a new factor involved in this process. Unlike many POL1 and POL12 mutations, which also cause telomere elongation, the pol12-216 mutation described here does not lead to either reduced Pol1 function, increased telomeric single-stranded DNA, or a reduction in telomeric gene silencing. Instead, and again unlike mutations affecting POL1, pol12-216 is lethal in combination with a mutation in the telomere end-binding and capping protein Stn1. Significantly, Pol12 and Stn1 interact in both two-hybrid and biochemical assays, and their synthetic-lethal interaction appears to be caused, at least in part, by a loss of telomere capping. These data reveal a novel function for Pol12 and a new connection between DNA polymerase ␣ and Stn1. We propose that Pol12, together with Stn1, plays a key role in linking telomerase action with the completion of lagging strand synthesis, and in a regulatory step required for telomere capping.

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“…In ⌬rif2 strains, telomeres elongate but remain well regulated. Previous studies have shown that Rif2p is particularly important in preventing the terminal telomeric tract from participating in the RAD52-dependent type II survivor pathway (Teng et al, 2000) and is also important in directly inhibiting telomerase addition to de novo cut telomeric ends (Diede and Gottschling, 1999). The known times in the cell cycle of in vivo telomeric DNA addition, late S phase and G2, coincide with when the ChIP association of Rif2p with telomeric DNA was lowest.…”

Section: A Model For Cell Cycle Regulation Of Telomeric Chromatinmentioning

confidence: 97%

“…Our model could explain this observed synergism. One possibility is that Rif1p plays a more structural role at the chromosome ends, whereas the primary role for Rif2p is to inhibit telomerase and recombination activities (Diede and Gottschling, 1999;Teng et al, 2000). Rif1p is considerably larger than Rif2p and associated 10 times more strongly with DNA than Rif2p in the ChIP assays (Figures 2B and 4B and C,left).…”

Section: A Model For Cell Cycle Regulation Of Telomeric Chromatinmentioning

confidence: 99%

Telomeric Protein Distributions and Remodeling Through the Cell Cycle inSaccharomyces cerevisiae

Smith

DeRisi

et al. 2003

MBoC

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In Saccharomyces cerevisiae, telomeric DNA is protected by a nonnucleosomal protein complex, tethered by the protein Rap1. Rif and Sir proteins, which interact with Rap1p, are thought to have further interactions with conventional nucleosomic chromatin to create a repressive structure that protects the chromosome end. We showed by microarray analysis that Rif1p association with the chromosome ends extends to subtelomeric regions many kilobases internal to the terminal telomeric repeats and correlates strongly with the previously determined genomic footprints of Rap1p and the Sir2-4 proteins in these regions. Although the end-protection function of telomeres is essential for genomic stability, telomeric DNA must also be copied by the conventional DNA replication machinery and replenished by telomerase, suggesting that transient remodeling of the telomeric chromatin might result in distinct protein complexes at different stages of the cell cycle. Using chromatin immunoprecipitation, we monitored the association of Rap1p, Rif1p, Rif2p, and the protein component of telomerase, Est2p, with telomeric DNA through the cell cycle. We provide evidence for dynamic remodeling of these components at telomeres. INTRODUCTIONTelomeres are nonnucleosomal protein-DNA complexes that prevent uncontrolled fusion, degradation, recombination, and elongation of chromosome ends (Muller, 1938;McClintock, 1941;Wright et al., 1992;Sandell and Zakian, 1993;Hande et al., 1999;Smith and Blackburn, 1999;Hackett et al., 2001). In Saccharomyces cerevisiae, terminal telomeric DNA is composed of ϳ350 base pairs of short, degenerate TG 1-3 repeats. One telomeric strand is polymerized by telomerase (Cohn and Blackburn, 1995) and forms an S-phasespecific TG 1-3 overhang (Wellinger et al., 1993(Wellinger et al., , 1996. The conventional DNA polymerase machinery is thought to synthesize the complementary C 1-3 A strand. Duplex telomeric DNA repeats are bound by the sequence-specific binding protein Rap1p, which recruits proteins Rif1p and Rif2p as well as Sir3p and Sir4p via its C-terminal domain (Moretti et al., 1994;Moazed and Johnson, 1996;Moretti and Shore, 2001).Telomeric regions in yeast also contain subtelomeric X-elements, which have only moderate homology to each other and are present at all chromosome ends, and the highly homologous YЈ elements located distal to the X elements (Chan and Tye, 1983) on about half of all chromosome ends. YЈ elements fall into 5.2-and 6.7-kb size classes (Louis and Haber, 1990;Louis and Haber, 1992), encode a helicase (Yamada et al., 1998), and are bounded by short (Ͻ150-base pair) tracts of internal telomeric TG 1-3 sequence DNA. Because YЈ elements often occur in tandem arrays of two to four repeats, these TG 1-3 tracts are found internal to the chromosome ends at distances depending upon the size class and number of YЈ elements present.The Rap1p, Ku, and Sir2-4 proteins are cross-linkable to DNA as far in as 3-15 kb from the chromosome end, consistent with their simultaneous binding to TG [1][2][3] repeat DNA ...

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Telomerase-Independent Lengthening of Yeast Telomeres Occurs by an Abrupt Rad50p-Dependent, Rif-Inhibited Recombinational Process

Abstract: cells eventually die (Lundblad and Szostak, 1989; Lendvay et al., 1996). However, a subset of the cells in cultures lacking telomerase continues to divide. These survivors do not arise in strains lacking Rad52p, a protein required for most homologous recombination events in

Cited by 102 publications

References 4 publications

PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase

PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase

Pol12, the B subunit of DNA polymerase α, functions in both telomere capping and length regulation

Telomeric Protein Distributions and Remodeling Through the Cell Cycle inSaccharomyces cerevisiae

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