TPP1 OB-fold Domain Controls Telomere Maintenance by Recruiting Telomerase to Chromosome Ends

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Aug 7

PMID 22863003

Citations 187

Authors

Franklin L Zhong

Luis F Z Batista

Adam Freund

Matthew F Pech

Andrew S Venteicher

Steven E Artandi

Affiliations

Soon will be listed here.

Abstract

Telomere synthesis in cancer cells and stem cells involves trafficking of telomerase to Cajal bodies, and telomerase is thought to be recruited to telomeres through interactions with telomere-binding proteins. Here, we show that the OB-fold domain of the telomere-binding protein TPP1 recruits telomerase to telomeres through an association with the telomerase reverse transcriptase TERT. When tethered away from telomeres and other telomere-binding proteins, the TPP1 OB-fold domain is sufficient to recruit telomerase to a heterologous chromatin locus. Expression of a minimal TPP1 OB-fold inhibits telomere maintenance by blocking access of telomerase to its cognate binding site at telomeres. We identify amino acids required for the TPP1-telomerase interaction, including specific loop residues within the TPP1 OB-fold domain and individual residues within TERT, some of which are mutated in a subset of pulmonary fibrosis patients. These data define a potential interface for telomerase-TPP1 interaction required for telomere maintenance and implicate defective telomerase recruitment in telomerase-related disease.

Citing Articles

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