A mechanism for telomere-specific telomere length regulation

Files

hdl_148847.pdf (3.08 MB)
  (Published version)

Date

2026

Authors

Teplitz, G.M.
Pasquier, E.
Bonnell, E.
De Laurentiis, E.
Bartle, L.
Lucier, J.F.
St-Laurent, G.
Dawson, D.S.
Wellinger, R.J.

Editors

Advisors

Journal Title

Journal ISSN

Volume Title

Type:

Journal article

Citation

Nucleic Acids Research (NAR), 2026; 54(1):gkaf1457-1-gkaf1457-13

Statement of Responsibility

Gabriela M Teplitz, Emeline Pasquier, Erin Bonnell, Evelina De Laurentiis, Louise Bartle, Jean-François Lucier, Gabriel St-Laurent, Dean S Dawson, Raymund J Wellinger

Conference Name

Abstract

Telomere length is a critical determinant of telomere function and hence chromosome stability. Critically short telomeres induce cellular senescence and division arrest, which eventually may lead to devastating age-related degenerative diseases. Conversely, maintenance of telomere length is a hallmark of cancer. How telomere set-length is established and molecular mechanisms for telomere-specific length regulation remained unknown. Here, we detail a mechanism of a telomere-specific set-length regulation that causes important differences in telomere length between individual telomeres in the same cell. Indeed, the results show that telomerase recruitment is modulated in cis in a telomere-specific way. Increased Sir4 abundance on yeast TEL03L subtelomeric heterochromatin leads to a set-length maintenance that is 1.5 to 2 times higher than on other telomeres. Remarkably, the distal 15 kb of TEL03L are sufficient to transfer this telomere-specific set-length regulation to another chromosome end. Furthermore, a mutation in the telomere boundary element protein Tbf1 allow increased Sir4 binding on telomeres and hence results in longer set-lengths. The results, therefore, will force a rethinking of telomere length regulation away from the generalized view that all telomeres are treated the same, to a more telomere-specific treatment.

School/Discipline

Dissertation Note

Provenance

Description

Available online 8 January 2026

Access Status

Rights

© The Author(s) 2026. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

License

Grant ID

Call number

Persistent link to this record