Human Molecular Genetics, Vol 7, 1137-1141, Copyright © 1998 by Oxford University Press
J Wen, YS Cong and S Bacchetti
Telomere shortening in human somatic cells and telomere maintenance in most
human immortal cell lines and tumours correlate respectively with the
absence and presence of telomerase, the enzyme that synthesizes telomeric
DNA de novo . However, approximately 30% of in vitro immortalized human
cell lines do not express this enzyme and maintain telomeres by an
alternative pathway (ALT) that may also operate in some tumours. Human
telomerase is a reverse transcriptase comprising minimally an RNA subunit
(hTER) and a catalytic protein moiety (hTERT). Normal somatic cells retain
expression of hTER but not of hTERT, and can be converted to a
telomerase-positive phenotype by ectopic expression of the catalytic
protein. We similarly have restored enzymatic activity to those ALT cell
lines that retain hTER expression. We also report that in those ALT cells
that are hTER negative, reintroduction of both hTER and hTERT is necessary
and sufficient for conversion to telomerase positivity. Moreover,
transfection of these cells with hTERT in conjunction with hTERs with a
mutated template results in the expression of an enzyme with altered
specificity. Reconstitution of telomerase activity in ALT cells,
particularly an activity capable of synthesizing mutant telomeric DNA, may
be exploited for the study of the ALT mechanism and its interaction with
the telomerase-dependent pathway, and for assessing the effects of mutant
telomeres on cell viability.
ARTICLES
Reconstitution of wild-type or mutant telomerase activity in telomerase- negative immortal human cells
Cancer Research Group, Department of Pathology, McMaster University Medical Center, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
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