Genomic instability in both wild-type and telomerase null MEFs

Ling Yang Hao, Carol W. Greider

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)62-68
Number of pages7
JournalChromosoma
Volume113
Issue number2
DOIs
StatePublished - Sep 1 2004

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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