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Telomeres and senescence
Author(s) -
Blackburn Elizabeth Helen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a890-d
Subject(s) - telomere , telomerase , ribonucleoprotein , telomerase rna component , senescence , rna , biology , telomerase reverse transcriptase , microbiology and biotechnology , cancer cell , cell growth , dna , cancer , cancer research , gene , genetics
Telomerase, a specialized ribonucleoprotein enzyme, both replenishes the DNA at telomeres, through its unique mechanism of internal RNA‐templated addition of telomeric DNA, and also protects the telomeres, thus counteracting cell senescence. Stem cells and the cells of systems that must be replenished or proliferate throughout life, such the immune system, contain telomerase in amounts that may be limiting. We have explored molecular features of the telomerase ribonucleoprotein needed for its capability to keep cells dividing, and also to protect telomeres. In human cancer cells, telomerase levels are commonly high. Previously, inhibition of telomerase enzymatic activity in cancer cells was predicted (and shown) to slow cell proliferation, but only following a delay requiring prior telomere shortening. Unexpectedly, we found that in the setting of human cancer cells, RNA interference‐mediated depletion of human telomerase RNA rapidly inhibited cell growth. These rapid effects occurred independently of telomere length, and without bulk telomere shortening or telomere uncapping, and did not require p53. Such telomerase RNA knock‐down in cancer cells induced a changed global gene expression profile indicative of a novel response pathway. These new findings also uncovered functions of telomerase in tumor growth and progression in addition to telomere maintenance.