Normal telomere maintenance in immortal ataxia telangiectasia cell lines.
Telomeres are maintained in germ line cells and immortal cell lines, but shorten with each cell division in most somatic cells. Blood lymphocytes from individuals with ataxia telangiectasia (AT) demonstrate an accelerated rate of telomere shortening and high levels of telomere associations. This accelerated loss of telomeres in somatic cells in AT could be due to either the loss of more telomeric DNA with every cell division or an increased rate of cell division. The gene for AT shares homology with the yeast TEL1 gene, in which mutations result in abnormally shortened telomeres. Thus, mutations in the gene for ataxia telangiectasia may also influence the ability of germ line cells and immortal cell lines to properly maintain telomere homeostasis. To investigate a possible defect of telomere maintenance in AT we have analyzed 8 simian virus 40 (SV40)-immortalized AT cell lines and twelve SV40-immortalized non-AT cell lines for both telomerase activity and telomere length. The results demonstrate that telomere length in AT cells is maintained via telomerase or an alternative (ALT) pathway in a manner indistinguishable from cell lines derived from normal cells. We also investigated telomere dynamics in one telomerase-positive AT cell line by analyzing the changes in the length of a single telomere, and found that this telomere maintained its equilibrium mean length (EML) similar to normal cell lines with stable chromosomes. The combined results show no significant differences between the telomeres of immortal AT and non-AT cell lines, demonstrating that the absence of wild-type ATM does not result in a fundamental defect in telomere maintenance in these cells.
Sprung
C N
CN
Radiation Oncology Research Laboratory, University of California, San Francisco 94103, USA.
Bryan
T M
TM
Reddel
R R
RR
Murnane
J P
JP
D001260:Ataxia Telangiectasia / Q000235:genetics / Q000473:pathology*; D002461:Cell Line, Transformed; D006801:Humans; D008214:Lymphocytes; D019098:Telomerase / Q000378:metabolism; D016615:Telomere
D019098:Telomerase