The influence of interstitial telomeric sequences on chromosome instability in human cells.
Although most telomere repeat sequences are found at the ends of chromosomes, some telomeric repeat sequences are also found at intrachromosomal locations in mammalian cells. Several studies have found that these interstitial telomeric repeat sequences can promote chromosome instability in rodent cells, either spontaneously or following ionizing radiation. In the present study we describe the extensive cytogenetic analysis of three different human cell lines with plasmids containing telomeric repeat sequences integrated at interstitial sites. In two of these cell lines, Q18 and P8SX, instability has been detected in the chromosome containing the integrated plasmid, involving breakage/fusion/bridge cycles or amplification of the plasmid DNA, respectively. However, the data suggest that the instability observed is characteristic of the general instability in these cell lines and that the telomeric repeat sequences themselves are not responsible. Consistent with this interpretation, the chromosome containing an integrated plasmid with 500 bp of telomeric repeat sequences is highly stable in the third cell line, SNG28, which has a relatively stable genome. The stability of the chromosome containing the integrated plasmid sequences in SNG28 makes this an excellent cell line to study the effect of ionizing radiation on the stability of interstitial telomeric sequences in human cells.
Desmaze
C
C
CEA, Laboratoire de Radiobiologie et Oncologie, DSV/DRR, Fontenay aux roses, France. CDesmaze@armoise.saclay.cea.fr
Alberti
C
C
Martins
L
L
Pottier
G
G
Sprung
C N
CN
Murnane
J P
JP
Sabatier
L
L
D002294:Carcinoma, Squamous Cell; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D002999:Clone Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D010957:Plasmids; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000737:chemistry* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured