Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 40900359

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

Rishi K Jaiswal·Teresa Garibo Domingo·Héloïse Grunchec·Komudi Singh·Mehdi Pirooznia·Eran Elhaik·Marita Cohn
View original source ↗Export metadata ↓

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 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.

Explore related subjects

TelomeraseTelomereSaccharomycetalesTelomere HomeostasisTelomere-Binding ProteinsTelomere ShorteningAlternative lengthening of telomeres (ALT)Budding yeast Naumovozyma castelliiGenome integritySubtelomeresTelomerase-independent telomere maintenanceJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rishi K Jaiswal, Teresa Garibo Domingo, Héloïse Grunchec, Komudi Singh, Mehdi Pirooznia, Eran Elhaik, Marita Cohn. 2025-09-03. Subtelomeric elements provide stability to short telomeres in telomerase-negative cells of the budding yeast Naumovozyma castellii.. https://doi.org/10.1007/s00294-025-01325-w

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2025

Aberrant TERT expression: linking chronic inflammation to hepatocellular carcinoma†.

Telomerase reverse transcriptase (TERT), the catalytic enzyme component of telomerase, plays multiple roles in cellular biology. Its canonical function is primarily associated with telomere maintenance and genomic stability. In addition, several studies revealed critical non-canonical extra-telomeric functions of TERT in various cellular processes, including cell proliferation and survival, DNA damage response, transcription, signal transduction, and metabolic regulation, both in normal and in cancer cells. Notably, TERT is aberrantly upregulated in more than 80% of hepatocellular carcinoma (HCC) cases, making it an important target in liver cancer research. However, due to the diversity and complexity of TERT's functions in vivo, the precise mechanisms by which TERT contributes to the initiation and progression of HCC remain unclear. A recent study published in The Journal of Pathology using the Alb-Cre;TertTg mouse model and clinical HCC samples addresses the role of TERT in hepatocarcinogenesis. The study demonstrates that TERT promotes cell cycle progression and hepatocarcinogenesis by enhancing NF-κB promoter activity and facilitating the ubiquitination of p21. Notably, absence of functional p53 accelerates liver tumor development in TERT transgenic mice. These findings further underscore the critical role of TERT in inflammation-driven hepatocarcinogenesis and provide new insights into its underlying mechanisms. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Telomerase↗