title: TZAP: A telomere-associated protein involved in telomere length control.
abstract: Telomeres are found at the end of chromosomes and are important for chromosome stability. Here we describe a specific telomere-associated protein: TZAP (telomeric zinc finger-associated protein). TZAP binds preferentially to long telomeres that have a low concentration of shelterin complex, competing with the telomeric-repeat binding factors TRF1 and TRF2. When localized at telomeres, TZAP triggers a process known as telomere trimming, which results in the rapid deletion of telomeric repeats. On the basis of these results, we propose a model for telomere length regulation in mammalian cells: The reduced concentration of the shelterin complex at long telomeres results in TZAP binding and initiation of telomere trimming. Binding of TZAP to long telomeres represents the switch that triggers telomere trimming, setting the upper limit of telomere length.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Julia Su Zhou
authors.identifier: 0000-0003-2737-4187
authors.initials: JS
authors.lastname: Li
authors.affiliation: Department of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.|Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Javier
authors.identifier: 0000-0001-8818-9650
authors.initials: J
authors.lastname: Miralles Fusté
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Tatevik
authors.identifier: 0000-0001-8917-6245
authors.initials: T
authors.lastname: Simavorian
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bartocci
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Tsai
authors.affiliation: Department of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Karlseder
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. edenchi@scripps.edu.
authors.forename: Eros
authors.identifier: 0000-0001-5378-4644
authors.initials: E
authors.lastname: Lazzerini Denchi
mesh_terms: D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D011485:Protein Binding; D020080:Tandem Repeat Sequences; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; C504753:TERF2 protein, human; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D014157:Transcription Factors; C100846:ZBTB48 protein, human