NASA Logo

NTRS

NTRS - NASA Technical Reports Server

Back to Results
TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell linesTelomere shortening in telomerase-negative somatic cells leads to the activation of the TP53 protein and the elimination of potentially unstable cells. We examined the effect of TP53 gene expression on both telomere metabolism and chromosome stability in immortal, telomerase-positive cell lines. Telomere length, telomerase activity, and chromosome instability were measured in multiple clones isolated from three related human B-lymphoblast cell lines that vary in TP53 expression; TK6 cells express wild-type TP53, WTK1 cells overexpress a mutant form of TP53, and NH32 cells express no TP53 protein. Clonal variations in both telomere length and chromosome stability were observed, and shorter telomeres were associated with higher levels of chromosome instability. The shortest telomeres were found in WTK1- and NH32-derived cells, and these cells had 5- to 10-fold higher levels of chromosome instability. The primary marker of instability was the presence of dicentric chromosomes. Aneuploidy and other stable chromosome alterations were also found in clones showing high levels of dicentrics. Polyploidy was found only in WTK1-derived cells. Both telomere length and chromosome instability fluctuated in the different cell populations with time in culture, presumably as unstable cells and cells with short telomeres were eliminated from the growing population. Our results suggest that transient reductions in telomere lengths may be common in immortal cell lines and that these alterations in telomere metabolism can have a profound effect on chromosome stability. Copyright 2000 Wiley-Liss, Inc.
Document ID
20040112592
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Schwartz, J. L.
(University of Washington Seattle, Washington 98195, United States)
Jordan, R.
Liber, H.
Murnane, J. P.
Evans, H. H.
Date Acquired
August 21, 2013
Publication Date
March 1, 2001
Publication Information
Publication: Genes, chromosomes & cancer
Volume: 30
Issue: 3
ISSN: 1045-2257
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: CA49696
CONTRACT_GRANT: CA69044
CONTRACT_GRANT: CA-73931
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Radiation Health

Available Downloads

There are no available downloads for this record.
No Preview Available