June 16, 2023|,

Preprint Highlight: Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere length maintenance

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Highlighted By: Huaiying Zhang, Carnegie Mellon University, Department of Biological Sciences

Preprint DOI: https://doi.org/https://doi.org/10.1101/2023.01.19.524780
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Significance Statement:

  • Dysfunctional telomeres in differentiated cells activate the ATM (ataxia telangiectasia-mutated)-dependent DNA damage response (DDR), leading to cell cycle arrest. However, the response of stem cells to telomere DNA damage remains poorly understood.
  • The authors used inducible expression of the nuclease FokI fused to the telomere protein TRF1 in human induced pluripotent stem cells (iPSCs), to induce acute DNA double-strand breaks specifically at iPSC telomeres. The authors observed an ATR (ataxia telangiectasia and Rad3-related)-dependent DDR and telomerase-independent telomere lengthening. This lengthening occurred through the alternative lengthening of telomeres (ALT) pathway, which relies on homology-directed DNA repair.
  • The study unveils a distinct response to telomere damage in iPSC cells and demonstrates that the ALT pathway, typically associated with telomerase-negative cancer cells, is active in telomerase-positive iPSC cells. These findings invite new hypotheses regarding the initiation of ALT-mediated cancer.

Read the Preprint:

Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere length maintenance
Katrina N Estep, John W Tobias, Rafael J Fernandez III, Brinley M Beveridge, F Brad Johnson
bioRxiv 2023.01.19.524780; doi: https://doi.org/10.1101/2023.01.19.524780

 

 

MBoC's Preprint Highlights are commentaries written by Early-Career Editors on recent preprints of interest. They do not constitute peer review or imply publication of the original preprint by MBoC. For more information, visit https://www.molbiolcell.org/curation-tools.

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