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Alternative Lengthening of Telomeres in the Budding Yeast Naumovozyma castellii

Cohn, Marita LU ; Karademir Andersson, Ahu LU ; Quintilla Mateo, Raquel and Carlsson Möller, Mirja LU (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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author
organization
publishing date
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
2020-07-08 05:05:52
@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},
}