Alternative Lengthening of Telomeres in the Budding Yeast Naumovozyma castellii
(2019) In G3: Genes, Genomes, Genetics 9(10). p.3345-3358- Abstract
- The enzyme telomerase ensures the integrity of linear chromosomes by maintaining telomere length. As a hallmark of cancer, cell immortalization and unlimited proliferation is gained by reactivation of telomerase. However, a significant fraction of cancer cells instead uses alternative telomere lengthening mechanisms toensuretelomere function,collectively known asAlternative Lengthening ofTelomeres(ALT). Although the budding yeast Naumovozyma castellii (Saccharomyces castellii) has a proficient telomerase activity, we demonstrate here that telomeres in N. castellii are efficiently maintained by a novel ALT mechanism after telomerase knockout. Remarkably, telomerase-negative cells proliferate indefinitely without any major growth crisis and... (More)
- The enzyme telomerase ensures the integrity of linear chromosomes by maintaining telomere length. As a hallmark of cancer, cell immortalization and unlimited proliferation is gained by reactivation of telomerase. However, a significant fraction of cancer cells instead uses alternative telomere lengthening mechanisms toensuretelomere function,collectively known asAlternative Lengthening ofTelomeres(ALT). Although the budding yeast Naumovozyma castellii (Saccharomyces castellii) has a proficient telomerase activity, we demonstrate here that telomeres in N. castellii are efficiently maintained by a novel ALT mechanism after telomerase knockout. Remarkably, telomerase-negative cells proliferate indefinitely without any major growth crisis and display wild-type colony morphology. Moreover, ALT cells maintain linear chromosomes and preserve a wild-type DNA organization at the chromosome termini, including a short stretch of terminal telomeric sequence. Notably, ALT telomeres are elongated by the addition of 275 bp repeats containing a short telomeric sequence and the subtelomeric DNA located just internally (TelKO element). Although telomeres may be elongated by several TelKO repeats, no dramatic genome-wide amplification occurs, thus indicating that the repeat addition may be regulated. Intriguingly, a short interstitial telomericsequence(ITS)functionsastheinitiationpointfortheadditionoftheTelKOelement.This implies that N. castellii telomeres are structurally predisposed to efficiently switch to the ALT mechanism as a response to telomerase dysfunction.
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Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/72d98fe1-33e0-43a2-9c60-69ebeac8531f
- author
- Cohn, Marita LU ; Karademir Andersson, Ahu LU ; Quintilla Mateo, Raquel and Carlsson Möller, Mirja LU
- organization
- publishing date
- 2019-10
- type
- Contribution to journal
- publication status
- published
- subject
- in
- G3: Genes, Genomes, Genetics
- volume
- 9
- issue
- 10
- pages
- 3345 - 3358
- publisher
- Genetics Society of America
- external identifiers
-
- scopus:85072993128
- pmid:31427453
- ISSN
- 2160-1836
- DOI
- 10.1534/g3.119.400428
- language
- English
- LU publication?
- yes
- id
- 72d98fe1-33e0-43a2-9c60-69ebeac8531f
- date added to LUP
- 2019-10-17 11:21:34
- date last changed
- 2024-03-04 13:31:53
@article{72d98fe1-33e0-43a2-9c60-69ebeac8531f, abstract = {{The enzyme telomerase ensures the integrity of linear chromosomes by maintaining telomere length. As a hallmark of cancer, cell immortalization and unlimited proliferation is gained by reactivation of telomerase. However, a significant fraction of cancer cells instead uses alternative telomere lengthening mechanisms toensuretelomere function,collectively known asAlternative Lengthening ofTelomeres(ALT). Although the budding yeast Naumovozyma castellii (Saccharomyces castellii) has a proficient telomerase activity, we demonstrate here that telomeres in N. castellii are efficiently maintained by a novel ALT mechanism after telomerase knockout. Remarkably, telomerase-negative cells proliferate indefinitely without any major growth crisis and display wild-type colony morphology. Moreover, ALT cells maintain linear chromosomes and preserve a wild-type DNA organization at the chromosome termini, including a short stretch of terminal telomeric sequence. Notably, ALT telomeres are elongated by the addition of 275 bp repeats containing a short telomeric sequence and the subtelomeric DNA located just internally (TelKO element). Although telomeres may be elongated by several TelKO repeats, no dramatic genome-wide amplification occurs, thus indicating that the repeat addition may be regulated. Intriguingly, a short interstitial telomericsequence(ITS)functionsastheinitiationpointfortheadditionoftheTelKOelement.This implies that N. castellii telomeres are structurally predisposed to efficiently switch to the ALT mechanism as a response to telomerase dysfunction.<br/>}}, author = {{Cohn, Marita and Karademir Andersson, Ahu and Quintilla Mateo, Raquel and Carlsson Möller, Mirja}}, issn = {{2160-1836}}, language = {{eng}}, number = {{10}}, pages = {{3345--3358}}, publisher = {{Genetics Society of America}}, series = {{G3: Genes, Genomes, Genetics}}, title = {{Alternative Lengthening of Telomeres in the Budding Yeast Naumovozyma castellii}}, url = {{http://dx.doi.org/10.1534/g3.119.400428}}, doi = {{10.1534/g3.119.400428}}, volume = {{9}}, year = {{2019}}, }