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Subtelomeric elements provide stability to short telomeres in telomerase-negative cells of the budding yeast Naumovozyma castellii

Jaiswal, Rishi K. LU ; Garibo Domingo, Teresa LU orcid ; Grunchec, Héloïse LU ; Singh, Komudi ; Pirooznia, Mehdi ; Elhaik, Eran LU orcid and Cohn, Marita LU (2025) In Current Genetics 71(1).
Abstract

Telomerase plays an important role in sustaining eukaryotic linear chromosomes, as elongation of telomeres is needed to counterbalance the shortening occurring in each replication round. Nevertheless, in telomerase-deficient cells, Alternative Lengthening of Telomeres (ALT) pathways can maintain telomeres by employing recombination-based mechanisms. In the budding yeast Naumovozyma castellii, effective activation of the ALT pathway leads to bypass of senescence and supports long-term growth. We found that telomere structures in N. castellii ALT cells are stably maintained at a shortened uniform length over extensive numbers of generations. This is correlated to the spreading of a subtelomeric sequence, TelKO element, to... (More)

Telomerase plays an important role in sustaining eukaryotic linear chromosomes, as elongation of telomeres is needed to counterbalance the shortening occurring in each replication round. Nevertheless, in telomerase-deficient cells, Alternative Lengthening of Telomeres (ALT) pathways can maintain telomeres by employing recombination-based mechanisms. In the budding yeast Naumovozyma castellii, effective activation of the ALT pathway leads to bypass of senescence and supports long-term growth. We found that telomere structures in N. castellii ALT cells are stably maintained at a shortened uniform length over extensive numbers of generations. This is correlated to the spreading of a subtelomeric sequence, TelKO element, to all telomeres. Genome sequencing of the wild-type strain revealed variants of the TelKO element, differing in their lengths, and separate ALT strains are maintained by spreading of distinct TelKO element variants. Although short uniform telomere structures are predominant, sporadic telomere lengthening events occur by addition of long repeated arrays of TelKO elements. The telomere-binding protein Rap1 can bind to TelKO sequences in vitro, indicating a functional role of TelKO elements in providing stability to shortened ALT telomeres. Our results suggest that stable maintenance and telomere functionality may be achieved by incorporating the distal subtelomeric TelKO sequences into the telomeric chromatin cap.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alternative lengthening of telomeres (ALT), Budding yeast Naumovozyma castellii, Genome integrity, Subtelomeres, Telomerase-independent telomere maintenance, Telomere
in
Current Genetics
volume
71
issue
1
article number
19
publisher
Springer Science and Business Media B.V.
external identifiers
  • scopus:105014906437
  • pmid:40900359
ISSN
0172-8083
DOI
10.1007/s00294-025-01325-w
language
English
LU publication?
yes
id
5af0be92-37c7-4ab4-8789-b40847330032
date added to LUP
2025-10-02 15:25:56
date last changed
2025-10-16 17:20:30
@article{5af0be92-37c7-4ab4-8789-b40847330032,
  abstract     = {{<p>Telomerase plays an important role in sustaining eukaryotic linear chromosomes, as elongation of telomeres is needed to counterbalance the shortening occurring in each replication round. Nevertheless, in telomerase-deficient cells, Alternative Lengthening of Telomeres (ALT) pathways can maintain telomeres by employing recombination-based mechanisms. In the budding yeast <i>Naumovozyma castellii</i>, effective activation of the ALT pathway leads to bypass of senescence and supports long-term growth. We found that telomere structures in <i>N. castellii</i> ALT cells are stably maintained at a shortened uniform length over extensive numbers of generations. This is correlated to the spreading of a subtelomeric sequence, TelKO element, to all telomeres. Genome sequencing of the wild-type strain revealed variants of the TelKO element, differing in their lengths, and separate ALT strains are maintained by spreading of distinct TelKO element variants. Although short uniform telomere structures are predominant, sporadic telomere lengthening events occur by addition of long repeated arrays of TelKO elements. The telomere-binding protein Rap1 can bind to TelKO sequences in vitro, indicating a functional role of TelKO elements in providing stability to shortened ALT telomeres. Our results suggest that stable maintenance and telomere functionality may be achieved by incorporating the distal subtelomeric TelKO sequences into the telomeric chromatin cap.</p>}},
  author       = {{Jaiswal, Rishi K. and Garibo Domingo, Teresa and Grunchec, Héloïse and Singh, Komudi and Pirooznia, Mehdi and Elhaik, Eran and Cohn, Marita}},
  issn         = {{0172-8083}},
  keywords     = {{Alternative lengthening of telomeres (ALT); Budding yeast Naumovozyma castellii; Genome integrity; Subtelomeres; Telomerase-independent telomere maintenance; Telomere}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Science and Business Media B.V.}},
  series       = {{Current Genetics}},
  title        = {{Subtelomeric elements provide stability to short telomeres in telomerase-negative cells of the budding yeast Naumovozyma castellii}},
  url          = {{http://dx.doi.org/10.1007/s00294-025-01325-w}},
  doi          = {{10.1007/s00294-025-01325-w}},
  volume       = {{71}},
  year         = {{2025}},
}