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Peer-reviewedCC BY-NC-ND 4.0Molecules and Cells

Divergent proteomic landscapes and functional requirements for telomere maintenance in type I and type II alternative lengthening of telomeres in mouse embryonic stem cells

  • Hyunji Lee1,2
  • Kyumin Park1,3
  • Sandrine Sauzet4
  • Subin Choi5
  • Seung Woo Cho5
  • Christine Hyein Chung1,2
  • Sanghyun Sung6
  • Dongan Kwon1,2
  • Hobum Song1,7
  • Serge Urbach8
  • Hiroyuki Niida9
  • Jérôme Déjardin4
1 more authors
  • Junho Lee1,2,10
10 affiliations
  1. 1Department of Biological Sciences, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea
  2. 2Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Korea
  3. 3Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
  4. 4Institute of Human Genetics, CNRS-University of Montpellier UMR 9002, 141 Cardonille Street, Montpellier 34000, France
  5. 5Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50, Ulju-gun, Ulsan 44919, Korea
  6. 6Aging Convergence Research Center (ACRC), Development and Differentiation Research Center, Korea Research Institute of Bioscience Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, South Korea
  7. 7Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
  8. 8Institute Genomics Functional, CNRS-University of Montpellier UMR 5203, 141 Cardonille Street, Montpellier 34000, France
  9. 9Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu city, Shizuoka 431-3192, Japan
  10. 10Research Institute of Basic Sciences, Seoul National University, Seoul 08826, Korea
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Abstract

Alternative lengthening of telomeres (ALT) is a telomerase-independent, recombination-based pathway utilized by some cancers. Previously, we established 2 distinct types of ALT survivors derived from mouse embryonic stem cells (mESCs), characterized by either a unique non-telomeric insertion (type I) or canonical telomeric repeats (type II). In this study, we used telomere-specific proteomics to elucidate the divergent telomere maintenance strategies of these ALT types. We identified distinct proteomic profiles enriched in type I versus type II ALT telomeres. ICE1 is a component of the Little Elongation Complex, which is specifically recruited to type I ALT telomeres, where it supports the transcription of telomeric repeat-containing RNA and telomere maintenance. In contrast, the serine/threonine kinase VRK2 is highly enriched in type II ALT telomeres, where it regulates telomere–nuclear envelope interactions. Depletion of ICE1 or VRK2 impairs telomere stability in type I and type II ALT mESCs, respectively. Our results indicate that cells with a common mESC origin can adopt distinct molecular mechanisms to maintain telomere integrity, highlighting the mechanistic heterogeneity of ALT telomere maintenance.

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Cite

BibTeXRIS
BibTeX
@article{lee2026divergent,
  title = {{Divergent proteomic landscapes and functional requirements for telomere maintenance in type I and type II alternative lengthening of telomeres in mouse embryonic stem cells}},
  author = {Hyunji Lee and Kyumin Park and Sandrine Sauzet and Subin Choi and Seung Woo Cho and Christine Hyein Chung and Sanghyun Sung and Dongan Kwon and Hobum Song and Serge Urbach and Hiroyuki Niida and Jérôme Déjardin and Junho Lee},
  journal = {Molecules and Cells},
  year = {2026},
  month = oct,
  doi = {10.1016/j.mocell.2026.100405},
  url = {https://doi.org/10.1016/j.mocell.2026.100405},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Divergent proteomic landscapes and functional requirements for telomere maintenance in type I and type II alternative lengthening of telomeres in mouse embryonic stem cells
AU  - Hyunji Lee
AU  - Kyumin Park
AU  - Sandrine Sauzet
AU  - Subin Choi
AU  - Seung Woo Cho
AU  - Christine Hyein Chung
AU  - Sanghyun Sung
AU  - Dongan Kwon
AU  - Hobum Song
AU  - Serge Urbach
AU  - Hiroyuki Niida
AU  - Jérôme Déjardin
AU  - Junho Lee
PY  - 2026
DA  - 2026/10/08
JO  - Molecules and Cells
DO  - 10.1016/j.mocell.2026.100405
UR  - https://doi.org/10.1016/j.mocell.2026.100405
AB  - Alternative lengthening of telomeres (ALT) is a telomerase-independent, recombination-based pathway utilized by some cancers. Previously, we established 2 distinct types of ALT survivors derived from mouse embryonic stem cells (mESCs), characterized by either a unique non-telomeric insertion (type I) or canonical telomeric repeats (type II). In this study, we used telomere-specific proteomics to elucidate the divergent telomere maintenance strategies of these ALT types. We identified distinct proteomic profiles enriched in type I versus type II ALT telomeres. ICE1 is a component of the Little Elongation Complex, which is specifically recruited to type I ALT telomeres, where it supports the transcription of telomeric repeat-containing RNA and telomere maintenance. In contrast, the serine/threonine kinase VRK2 is highly enriched in type II ALT telomeres, where it regulates telomere–nuclear envelope interactions. Depletion of ICE1 or VRK2 impairs telomere stability in type I and type II ALT mESCs, respectively. Our results indicate that cells with a common mESC origin can adopt distinct molecular mechanisms to maintain telomere integrity, highlighting the mechanistic heterogeneity of ALT telomere maintenance.
SN  - 1016-8478
SN  - 0219-1032
ER  -