Telomerase maintains telomere structure in normal human cells.
In normal human cells, telomeres shorten with successive rounds of cell division, and immortalization correlates with stabilization of telomere length. These observations suggest that human cancer cells achieve immortalization in large part through the illegitimate activation of telomerase expression. Here, we demonstrate that the rate-limiting telomerase catalytic subunit hTERT is expressed in cycling primary presenescent human fibroblasts, previously believed to lack hTERT expression and telomerase activity. Disruption of telomerase activity in normal human cells slows cell proliferation, restricts cell lifespan, and alters the maintenance of the 3' single-stranded telomeric overhang without changing the rate of overall telomere shortening. Together, these observations support the view that telomerase and telomere structure are dynamically regulated in normal human cells and that telomere length alone is unlikely to trigger entry into replicative senescence.
Masutomi
Kenkichi
K
Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Yu
Evan Y
EY
Khurts
Shilagardy
S
Ben-Porath
Ittai
I
Currier
Jennifer L
JL
Metz
Geoffrey B
GB
Brooks
Mary W
MW
Kaneko
Shuichi
S
Murakami
Seishi
S
DeCaprio
James A
JA
Weinberg
Robert A
RA
Stewart
Sheila A
SA
Hahn
William C
WC
D000911:Antibodies, Monoclonal / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002472:Cell Transformation, Viral / Q000235:genetics; D004261:DNA Replication; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009154:Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D019098:Telomerase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019098:Telomerase