Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Moreno, SP; Fuste, JM; Kaiser, M; Li, JSZ; Nassour, J; Haggblom, C; Denchi, EL; Karlseder, J.
TZAP overexpression induces telomere dysfunction and ALT-like activity in ATRX/DAXX-deficient cells
ISCIENCE. 2023; 26(4): 106405
Doi: 10.1016/j.isci.2023.106405
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- Co-authors Med Uni Graz
- Kaiser Melanie
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- Abstract:
- The appropriate regulation of telomere length homeostasis is crucial for the maintenance of genome integrity. The telomere-binding protein TZAP has been suggested to regulate telomere length by promoting t-circle and c-circle excisions through telomere trimming, yet the molecular mechanisms by which TZAP functions at telomeres are not understood. Using a system based on TZAP overexpression, we show that efficient TZAP recruitment to telomeres occurs in the context of open telomeric chromatin caused by loss of ATRX/DAXX independently of H3.3 deposition. Moreover, our data indicate that TZAP binding to telomeres induces telomere dysfunction and ALT-like activity, resulting in the generation of t-circles and c-circles in a Bloom-Topoisomerase III alpha-RMI1-RMI2 (BTR)-dependent manner.