Telomerase Promotes Formation of a Telomere Protective Complex in Cancer Cells

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2019 Oct 17

PMID 31616780

Citations 20

Authors

Omesha N Perera

Alexander P Sobinoff

Erdahl T Teber

Ashley Harman

Michelle F Maritz

Sile F Yang

Hilda A Pickett

Anthony J Cesare

Jonathan W Arthur

Karen L Mackenzie

Tracy M Bryan

Affiliations

Soon will be listed here.

Abstract

Telomerase is a ribonucleoprotein complex that catalyzes addition of telomeric DNA repeats to maintain telomeres in replicating cells. Here, we demonstrate that the telomerase protein hTERT performs an additional role at telomeres that is independent of telomerase catalytic activity yet essential for telomere integrity and cell proliferation. Short-term depletion of endogenous hTERT reduced the levels of heat shock protein 70 (Hsp70-1) and the telomere protective protein Apollo at telomeres, and induced telomere deprotection and cell cycle arrest, in the absence of telomere shortening. Short-term expression of hTERT promoted colocalization of Hsp70-1 with telomeres and Apollo and reduced numbers of deprotected telomeres, in a manner independent of telomerase catalytic activity. These data reveal a previously unidentified noncanonical function of hTERT that promotes formation of a telomere protective complex containing Hsp70-1 and Apollo and is essential for sustained proliferation of telomerase-positive cancer cells, likely contributing to the known cancer-promoting effects of both hTERT and Hsp70-1.

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