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

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Science  10 Feb 2017:
Vol. 355, Issue 6325, pp. 638-641
DOI: 10.1126/science.aah6752

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A protein to trim too-long telomeres

Telomeres cap the ends of linear eukaryotic chromosomes. They consist of multiple copies of short DNA repeats. The length of telomeres is important to genome stability; if they become too short, individuals can become prone to cancer and premature aging. Li et al. discovered a protein, TZAP (telomeric zinc finger–associated protein), which instead prevents telomeres from becoming too long (see the Perspective by Lossaint and Lingner). TZAP binds directly to the telomeric DNA repeats, competing with the shelterin complex. It stimulates telomere trimming, preventing aberrantly long telomeres.

Science, this issue p. 638; see also p. 578

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.

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