TZAP overexpression induces telomere dysfunction and ALT-like activity in ATRX/DAXX-deficient cells.

Autor:	Moreno SP; The Salk Institute for Biological Studies, Molecular and Cell Biology Department, 10010 N. Torrey pines Road, La Jolla, CA 92037, USA., Fusté JM; The Salk Institute for Biological Studies, Molecular and Cell Biology Department, 10010 N. Torrey pines Road, La Jolla, CA 92037, USA., Kaiser M; The Salk Institute for Biological Studies, Molecular and Cell Biology Department, 10010 N. Torrey pines Road, La Jolla, CA 92037, USA., Li JSZ; The Ludwig Institute for Cancer Research, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA., Nassour J; The Salk Institute for Biological Studies, Molecular and Cell Biology Department, 10010 N. Torrey pines Road, La Jolla, CA 92037, USA., Haggblom C; The Salk Institute for Biological Studies, Molecular and Cell Biology Department, 10010 N. Torrey pines Road, La Jolla, CA 92037, USA., Denchi EL; Laboratory for Genome Integrity, National Cancer Institute, Building 37, Room 2144B, Bethesda, MD 20892, USA., Karlseder J; The Salk Institute for Biological Studies, Molecular and Cell Biology Department, 10010 N. Torrey pines Road, La Jolla, CA 92037, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Mar 14; Vol. 26 (4), pp. 106405. Date of Electronic Publication: 2023 Mar 14 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.106405
Abstrakt:	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 IIIα-RMI1-RMI2 (BTR)-dependent manner. Competing Interests: The authors declare no competing interests. (© 2023 The Author(s).)
Databáze:	MEDLINE
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