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.
journal_name
Sci Advjournal_title
Science advancesauthors
Perera ON,Sobinoff AP,Teber ET,Harman A,Maritz MF,Yang SF,Pickett HA,Cesare AJ,Arthur JW,MacKenzie KL,Bryan TMdoi
10.1126/sciadv.aav4409subject
Has Abstractpub_date
2019-10-02 00:00:00pages
eaav4409issue
10issn
2375-2548pii
aav4409journal_volume
5pub_type
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