PMID- 15258806 OWN - NLM STAT- MEDLINE DCOM- 20050429 LR - 20181113 IS - 0009-5915 (Print) IS - 0009-5915 (Linking) VI - 113 IP - 2 DP - 2004 Sep TI - Genomic instability in both wild-type and telomerase null MEFs. PG - 62-8 AB - 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 gamma-H2AX phosphorylation in response to irradiation, indicating a loss of DNA damage checkpoints. FAU - Hao, Ling-Yang AU - Hao LY AD - Graduate Program in Human Genetics, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA. FAU - Greider, Carol W AU - Greider CW LA - eng GR - CA16519/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040716 PL - Austria TA - Chromosoma JT - Chromosoma JID - 2985138R RN - 0 (Histones) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (gamma-H2AX protein, mouse) SB - IM MH - Animals MH - Cell Line MH - DNA Damage/genetics/physiology/radiation effects MH - Embryo, Mammalian/cytology/*physiology MH - Fibroblasts/*physiology MH - Gamma Rays MH - Gene Deletion MH - Genomic Instability/genetics/*physiology/radiation effects MH - Histones/genetics MH - Mice MH - Mice, Knockout MH - Radiation Tolerance/genetics/*physiology/radiation effects MH - Telomere/genetics/metabolism MH - Tumor Suppressor Protein p53/genetics/metabolism EDAT- 2004/07/20 05:00 MHDA- 2005/04/30 09:00 CRDT- 2004/07/20 05:00 PHST- 2004/03/25 00:00 [received] PHST- 2004/05/06 00:00 [revised] PHST- 2004/05/09 00:00 [accepted] PHST- 2004/07/20 05:00 [pubmed] PHST- 2005/04/30 09:00 [medline] PHST- 2004/07/20 05:00 [entrez] AID - 10.1007/s00412-004-0291-7 [doi] PST - ppublish SO - Chromosoma. 2004 Sep;113(2):62-8. doi: 10.1007/s00412-004-0291-7. Epub 2004 Jul 16.