Abstract
To examine chromosome instability in the absence of telomerase, we established mouse embryonic fibroblast (MEF) lines from late generation mTR-/- and wild-type animals and examined metaphases using telomere fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY). In early passages, mTR-/-G6 cell lines showed more chromosome ends with no telomere signal, more chromosome end-to-end fusions and greater radiosensitivity than wild-type lines. At later passages, however, the rate of genomic instability in the wild-type MEFs increased to a level similar or higher than seen in the mTR-/- G6 cell lines. This high degree of instability in wild-type MEF lines suggests that post-crisis MEFs should not be considered genetically defined cell lines. Surprisingly, the increased radiosensitivity seen in early passage mTR-/- G6 cultures was lost after crisis. Both post-crisis mTR-/- G6 MEFs and wild-type MEFs showed loss of p53 and γ-H2AX phosphorylation in response to irradiation, indicating a loss of DNA damage checkpoints.
Original language | English (US) |
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Pages (from-to) | 62-68 |
Number of pages | 7 |
Journal | Chromosoma |
Volume | 113 |
Issue number | 2 |
DOIs | |
State | Published - Sep 2004 |
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)