Here, we describe a novel specific telomere-associated protein: TZAP (Telomeric Zinc finger-Associated Protein). TZAP binds preferentially to long telomeres that have a low concentration of shelterin complex, in virtue of competition with the telomeric repeat binding factors TRF1 and TRF2. When localized at telomeres, TZAP triggers “telomere trimming”, a process that results in the rapid deletion of telomeric repeats. Based on these results, we propose a novel model for telomere length regulation in mammalian cells. Binding of TZAP to telomeres is restricted to long telomeres and represents the switch that triggers telomere trimming, setting the upper limit of telomere length. In this model, the reduced concentration of the shelterin complex at long telomeres results in TZAP binding and initiation of telomere trimming.

Affective temperaments contribute to smoking initiation and maintenance independently of age, education, and depression. The significant contribution of depressive temperament in males and irritable temperament in females may highlight the role of gender-discordant temperaments in vulnerable subgroups.

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