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Science. 2017 Feb 10;355(6325):638-641. doi: 10.1126/science.aah6752. Epub 2017 Jan 12.

TZAP: A telomere-associated protein involved in telomere length control.

Author information

1
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Department of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
3
Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
4
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. edenchi@scripps.edu.

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.

PMID:
28082411
PMCID:
PMC5518674
DOI:
10.1126/science.aah6752
[Indexed for MEDLINE]
Free PMC Article

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