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Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast
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Zeitschriftentitel: | The Journal of Cell Biology |
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Personen und Körperschaften: | , |
In: | The Journal of Cell Biology, 145, 1999, 2, S. 203-214 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Rockefeller University Press
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Schlagwörter: |
author_facet |
Smith, Christopher D. Blackburn, Elizabeth H. Smith, Christopher D. Blackburn, Elizabeth H. |
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author |
Smith, Christopher D. Blackburn, Elizabeth H. |
spellingShingle |
Smith, Christopher D. Blackburn, Elizabeth H. The Journal of Cell Biology Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast Cell Biology |
author_sort |
smith, christopher d. |
spelling |
Smith, Christopher D. Blackburn, Elizabeth H. 0021-9525 1540-8140 Rockefeller University Press Cell Biology http://dx.doi.org/10.1083/jcb.145.2.203 <jats:p>Telomeres are the protein–nucleic acid structures at the ends of eukaryote chromosomes. Tandem repeats of telomeric DNA are templated by the RNA component (TER1) of the ribonucleoprotein telomerase. These repeats are bound by telomere binding proteins, which are thought to interact with other factors to create a higher-order cap complex that stabilizes the chromosome end. In the budding yeast Kluyveromyces lactis, the incorporation of certain mutant DNA sequences into telomeres leads to uncapping of telomeres, manifested by dramatic telomere elongation and increased length heterogeneity (telomere deregulation). Here we show that telomere deregulation leads to enlarged, misshapen “monster” cells with increased DNA content and apparent defects in cell division. However, such deregulated telomeres became stabilized at their elongated lengths upon addition of only a few functionally wild-type telomeric repeats to their ends, after which the frequency of monster cells decreased to wild-type levels. These results provide evidence for the importance of the most terminal repeats at the telomere in maintaining the cap complex essential for normal telomere function. Analysis of uncapped and capped telomeres also show that it is the deregulation resulting from telomere uncapping, rather than excessive telomere length per se, that is associated with DNA aberrations and morphological defects.</jats:p> Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast The Journal of Cell Biology |
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1999 |
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Rockefeller University Press |
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The Journal of Cell Biology |
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title |
Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_unstemmed |
Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_full |
Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_fullStr |
Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_full_unstemmed |
Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_short |
Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_sort |
uncapping and deregulation of telomeres lead to detrimental cellular consequences in yeast |
topic |
Cell Biology |
url |
http://dx.doi.org/10.1083/jcb.145.2.203 |
publishDate |
1999 |
physical |
203-214 |
description |
<jats:p>Telomeres are the protein–nucleic acid structures at the ends of eukaryote chromosomes. Tandem repeats of telomeric DNA are templated by the RNA component (TER1) of the ribonucleoprotein telomerase. These repeats are bound by telomere binding proteins, which are thought to interact with other factors to create a higher-order cap complex that stabilizes the chromosome end. In the budding yeast Kluyveromyces lactis, the incorporation of certain mutant DNA sequences into telomeres leads to uncapping of telomeres, manifested by dramatic telomere elongation and increased length heterogeneity (telomere deregulation). Here we show that telomere deregulation leads to enlarged, misshapen “monster” cells with increased DNA content and apparent defects in cell division. However, such deregulated telomeres became stabilized at their elongated lengths upon addition of only a few functionally wild-type telomeric repeats to their ends, after which the frequency of monster cells decreased to wild-type levels. These results provide evidence for the importance of the most terminal repeats at the telomere in maintaining the cap complex essential for normal telomere function. Analysis of uncapped and capped telomeres also show that it is the deregulation resulting from telomere uncapping, rather than excessive telomere length per se, that is associated with DNA aberrations and morphological defects.</jats:p> |
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author | Smith, Christopher D., Blackburn, Elizabeth H. |
author_facet | Smith, Christopher D., Blackburn, Elizabeth H., Smith, Christopher D., Blackburn, Elizabeth H. |
author_sort | smith, christopher d. |
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description | <jats:p>Telomeres are the protein–nucleic acid structures at the ends of eukaryote chromosomes. Tandem repeats of telomeric DNA are templated by the RNA component (TER1) of the ribonucleoprotein telomerase. These repeats are bound by telomere binding proteins, which are thought to interact with other factors to create a higher-order cap complex that stabilizes the chromosome end. In the budding yeast Kluyveromyces lactis, the incorporation of certain mutant DNA sequences into telomeres leads to uncapping of telomeres, manifested by dramatic telomere elongation and increased length heterogeneity (telomere deregulation). Here we show that telomere deregulation leads to enlarged, misshapen “monster” cells with increased DNA content and apparent defects in cell division. However, such deregulated telomeres became stabilized at their elongated lengths upon addition of only a few functionally wild-type telomeric repeats to their ends, after which the frequency of monster cells decreased to wild-type levels. These results provide evidence for the importance of the most terminal repeats at the telomere in maintaining the cap complex essential for normal telomere function. Analysis of uncapped and capped telomeres also show that it is the deregulation resulting from telomere uncapping, rather than excessive telomere length per se, that is associated with DNA aberrations and morphological defects.</jats:p> |
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spelling | Smith, Christopher D. Blackburn, Elizabeth H. 0021-9525 1540-8140 Rockefeller University Press Cell Biology http://dx.doi.org/10.1083/jcb.145.2.203 <jats:p>Telomeres are the protein–nucleic acid structures at the ends of eukaryote chromosomes. Tandem repeats of telomeric DNA are templated by the RNA component (TER1) of the ribonucleoprotein telomerase. These repeats are bound by telomere binding proteins, which are thought to interact with other factors to create a higher-order cap complex that stabilizes the chromosome end. In the budding yeast Kluyveromyces lactis, the incorporation of certain mutant DNA sequences into telomeres leads to uncapping of telomeres, manifested by dramatic telomere elongation and increased length heterogeneity (telomere deregulation). Here we show that telomere deregulation leads to enlarged, misshapen “monster” cells with increased DNA content and apparent defects in cell division. However, such deregulated telomeres became stabilized at their elongated lengths upon addition of only a few functionally wild-type telomeric repeats to their ends, after which the frequency of monster cells decreased to wild-type levels. These results provide evidence for the importance of the most terminal repeats at the telomere in maintaining the cap complex essential for normal telomere function. Analysis of uncapped and capped telomeres also show that it is the deregulation resulting from telomere uncapping, rather than excessive telomere length per se, that is associated with DNA aberrations and morphological defects.</jats:p> Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast The Journal of Cell Biology |
spellingShingle | Smith, Christopher D., Blackburn, Elizabeth H., The Journal of Cell Biology, Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast, Cell Biology |
title | Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_full | Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_fullStr | Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_full_unstemmed | Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_short | Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
title_sort | uncapping and deregulation of telomeres lead to detrimental cellular consequences in yeast |
title_unstemmed | Uncapping and Deregulation of Telomeres Lead to Detrimental Cellular Consequences in Yeast |
topic | Cell Biology |
url | http://dx.doi.org/10.1083/jcb.145.2.203 |