Everything You Ever Wanted to Know About <i>Saccharomyces cerevisiae</i> Telomeres: Beginning to End

Wellinger, Raymund J.; Zakian, Virginia A.

doi:10.1534/genetics.111.137851

Cited by 309 publications

(457 citation statements)

References 360 publications

(668 reference statements)

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“…T elomeres are dynamic DNA-protein complexes that protect the ends of linear chromosomes, prevent detrimental chromosome rearrangements and defend against genomic instability and the associated risk of cancer [1][2][3][4][5] . Telomeres, consisting of tandem repeats of short G-rich sequences, are synthesized by the enzyme telomerase 6,7 .…”

mentioning

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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mentioning

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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“…The budding yeast Saccharomyces cerevisiae telomeres are relatively short (300 ± 75 bp), consisting of repeats of the form (G 1-3 T) n •(AC 1-3 ) n (1). Telomeric DNA normally is bound by a multiprotein capping complex that is essential to maintain the integrity of telomeres, protecting them from DNA repair and recombination (1).…”

mentioning

confidence: 99%

Genome rearrangements caused by interstitial telomeric sequences in yeast

Aksenova

Greenwell

Dominska

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

106

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Significance Telomeres are composed of simple repetitive DNA sequences that normally are located at the ends of the chromosomes. Occasionally, however, they also are found inside chromosomes. Some of these internal or interstitial telomeric sequences colocalize with chromosomal fragile sites, preferred sites of breakage in some cancers and hereditary human diseases. The mechanisms responsible for genome instability at interstitial telomeric sequences are unclear. We developed a system to study genetic instabilities caused by these sequences in a model organism (baker’s yeast) that allowed us to characterize various chromosomal rearrangements and to measure the likelihood of their formation. We found that interstitial telomeric sequences promote the formation of deletions, duplications, inversions, and translocations, and we proposed molecular mechanisms responsible for these events.

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“…United we stand, divided we fall Franck Gallardo, 1, * Nancy Laterreur, 2 Raymund J. Wellinger 2 DNA shortens during each round of cell division and eventually this failure to maintain telomeric repeats triggers replicative senescence and permanent cell cycle arrest. In order to counteract this telomere attrition, virtually all eukaryotic cells contain an end specialized enzyme called telomerase.…”

Section: Telomerase Caught In the Actmentioning

confidence: 99%

“…4 In budding yeast, the RNA component of telomerase is called TLC1 and is used as a scaffold for the binding of the catalytic subunit (Est2) and several regulatory proteins, such as Est1, Est3 and the yKu70/80 complex. 2,[5][6][7][8] However, despite the fact that a TLC1 RNA/Est2 complex is sufficient for telomerase activity in vitro, activity in vivo requires other regulatory proteins and cell cycle-dependent post-translational modifications on some of them. These ideas have been well characterized during the last decade as it became clear that telomerase is active only in late S-phase on telomeres.…”

Section: Telomerase Caught In the Actmentioning

confidence: 99%

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Telomerase caught in the act

et al. 2012

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T he stable linearity of eukaryotic chromosomes depends on special characteristics of their ends, the telomeres. Accurate telomere function in turn requires a sustained presence of repeated DNA elements, which are maintained by the enzyme telomerase. The telomerase holoenzyme is composed of both protein and RNA, and its functions rely on proper expression, maturation, trafficking and assembly of these components. Conflicting models for the recruitment of telomerase at telomeres have been proposed; one suggests a local activation of telomerase at short telomeres, while the other proposes that telomerase is recruited only at short telomeres. To discriminate between these models and investigate the cell cycle-dependent regulation of telomerase in living cells, a GFP reporter system to visualize the yeast telomerase RNA has been recently developed. This assay shed new light on the mechanism of recruitment of telomerase to telomeres, and it uncovered a hitherto unrecognized mechanism for restricting telomerase access to telomeres.

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Everything You Ever Wanted to Know About Saccharomyces cerevisiae Telomeres: Beginning to End

Cited by 309 publications

References 360 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

Genome rearrangements caused by interstitial telomeric sequences in yeast

Telomerase caught in the act

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