NORMAL TELOMERE MAINTENANCE IN IMMORTAL ATAXIA-TELANGIECTASIA CELL-LINES

Telomeres are maintained in germ line cells and immortal cell lines, b ut shorten with each cell division in most somatic cells. Blood lympho cytes from individuals with ataxia telangiectasia (AT) demonstrate an accelerated rate of telomere shortening and high levels of telomere as sociations, 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 abnor mally shortened telomeres, Thus, mutations in the gene for ataxia tela ngiectasia may also influence the ability of germ line cells and immor tal cell lines to properly maintain telomere homeostasis, To investiga te a possible defect of telomere maintenance in AT we have analyzed 8 simian virus 40 (SV40)-immortalized AT cell lines and twelve SV40-immo rtalized non-AT cell lines for both telomerase activity and telomere l ength. The results demonstrate that telomere length in AT cells is mai ntained via telomerase or an alternative (ALT) pathway in a manner ind istinguishable from cell lines derived from normal cells, We also inve stigated telomere dynamics in one telomerase-positive AT cell line by analyzing the changes in the length of a single telomere, and found th at this telomere maintained its equilibrium mean length (EML) similar to normal cell lines with stable chromosomes, The combined results sho w no significant differences between the telomeres of immortal AT and non-AT cell lines, demonstrating that the absence of wild-type ATM doe s not result in a fundamental defect in telomere maintenance in these cells. (C) 1997 Elsevier Science B.V.