The influence of interstitial telomeric sequences on chromosome instability in human cells

Abstract

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.

Insertion of Telomeric Repeats at Intrachromosomal Break Sites During Primate Evolution

“…It has been suggested that ITSs are preferential sites of breakage (Bertoni et al 1994(Bertoni et al , 1996Desmaze et al 1999); the conclusions derived from the present work support instead the hypothesis that the short primate ITSs are relics of ancient breakage within fragile sites rather than fragile sites themselves.…”

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

“…We performed TRF1 and TRF2m ChIP-qPCR in the SNG28 human squamous carcinoma cell line. This cell line contains an artificially integrated 800-bp telomeric sequence in the middle of the long arm of chromosome 4 (named 4qITS) [26,30], which serves as a positive control for the immunoprecipitations. We observed a clear TRF1 and TRF2 enrichment for five out of five identified TRF binding sites and also of the 4qITS sequence ( Figure 3).…”

Interstitial Telomere-like Repeats in the Haplopappus gracilis (Asteraceae) Genome Revealed by Fluorescence in situ Hybridization

“…In human chromosomes, the presence of ITR induces chromosome instability, resulting in spontaneous or artificial chromosome rearrangement (Park et al 1992, Boutouil et al 1996, Slijepcevic et al 1996, Desmaze et al 1999. Ames and Mitra (1968) and Hanmoto et al (2003) reported that the subdistal positions of the long arms in both 1g and 2g chromosomes of H. gracilis are the breakage points by maleic hydrazide treatment and by ionizing radiation, respectively.…”