Intracellular trafficking of yeast telomerase components
TLDR
It is found that Est1p, Est2p and TLC1 can migrate independently of each other to the nucleus and a role of the nucleolus in telomerase biogenesis is suggested.Abstract:
Telomerase uses an internal RNA moiety as template for the synthesis of telomere repeats. In Saccharomyces cerevisiae, the telomerase holoenzyme contains the telomerase reverse transcriptase subunit Est2p, the telomerase RNA moiety TLC1, the telomerase associated proteins Est1p and Est3p, and Sm proteins. Here we assess telomerase assembly by determining the localization of telomerase components. We found that Est1p, Est2p and TLC1 can migrate independently of each other to the nucleus. With limiting amounts of TLC1, overexpressed Est1p and Est2p accumulated in the nucleolus, whereas enzymatically active Est2p–TLC1 complexes are distributed over the entire nucleus. The distribution to the nucleoplasm depended on the specific interaction between Est2p and TLC1 but was independent of Est1p and Est3p. Altogether, our results suggest a role of the nucleolus in telomerase biogenesis. We also describe experiments that support a transient cytoplasmic localization of TLC1 RNA.read more
Citations
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Journal ArticleDOI
Getting to the end: telomerase access in yeast and humans
TL;DR: In organisms with linear chromosomes, telomeres are essential to maintain genome integrity, however, inappropriate telomere addition, for example to double-stranded DNA breaks, might stabilize deleterious genetic changes.
Journal ArticleDOI
Low abundance of telomerase in yeast: implications for telomerase haploinsufficiency.
Amy D. Mozdy,Thomas R. Cech +1 more
TL;DR: The finding that yeast telomerase may be outnumbered by its telomeric DNA substrates provides a new perspective for interpreting the results of telomere maintenance studies.
Journal ArticleDOI
Arabidopsis POT1A interacts with TERT-V(I8), an N-terminal splicing variant of telomerase.
TL;DR: This interaction indicates possible mechanisms for telomerase regulation by alternative splicing and by POT1 proteins, suggesting a specific role for this paralogue in the Arabidopsis genome.
Journal ArticleDOI
TLC1 RNA nucleo-cytoplasmic trafficking links telomerase biogenesis to its recruitment to telomeres
TL;DR: The results reveal that the nucleo‐cytoplasmic trafficking of the TLC1 RNA is an important step in telomere homeostasis, and link telomerase biogenesis to its recruitment to telomeres.
Journal ArticleDOI
Telomere maintenance and DNA replication: how closely are these two connected?
TL;DR: Recent findings on the interactions between the conventional replication machinery and telomere replication are described and how DNA-integrity checkpoints might impinge on both the processing of the telomeric DNA ends and the establishment of the DNA end structure required for end protection and genome stability are discussed.
References
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Journal ArticleDOI
A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis.
TL;DR: The essential RNA component of this ribonucleoprotein enzyme has now been cloned and found to contain the sequence CAACCCCAA, which seems to be the template for the synthesis of TTGGGG repeats.
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Reverse Transcriptase Motifs in the Catalytic Subunit of Telomerase
Joachim Lingner,Timothy P. Hughes,Andrej Shevchenko,Matthias Mann,Victoria Lundblad,Thomas R. Cech +5 more
TL;DR: The reverse transcriptase protein fold, previously known to be involved in retroviral replication and retrotransposition, is essential for normal chromosome telomere replication in diverse eukaryotes.
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A telomerase component is defective in the human disease dyskeratosis congenita
TL;DR: It is found that primary fibroblasts and lymphoblasts from DKC-affected males are not detectably deficient in conventional H/ACA small nucleolar RNA accumulation or function; however, DKC cells have a lower level of telomerase RNA, produce lower levels of telomersase activity and have shorter telomeres than matched normal cells.
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A mutant with a defect in telomere elongation leads to senescence in yeast.
TL;DR: Using this assay, a mutant that displays a progressive decrease in telomere length as well as an increased frequency of chromosome loss is isolated, which defines a new gene, designated EST1 (for ever shorter telomeres).
Journal ArticleDOI
Ribosome synthesis in Saccharomyces cerevisiae.
J. Venema,David Tollervey +1 more
TL;DR: The recent, and often surprising, advances in the understanding of ribosome synthesis in the yeast Saccharomyces cerevisiae will underscore the unexpected complexity of eukaryotic ribosomes synthesis.