Human telomeres: fusion and interstitial sites

doi:10.1016/0168-9525(89)90137-6

Trends in Genetics

Volume 5, 1989, Pages 326-331

https://doi.org/10.1016/0168-9525(89)90137-6 Get rights and content

Abstract

The ends of human chromosomes have been shown recently to resemble those of simple organisms. With this in mind, we discuss the nature and possible significance of rare chromosome fusion events thought to involve telomeres, particularly those fusion events found in some tumours. Also we argue that interstitial telomere-like stretches may be particularly prone to recombination, breakage and fragility.

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Cited by (248)

Expansion of Interstitial Telomeric Sequences in Yeast
2015, Cell Reports
Citation Excerpt :
They are believed to result from the insertions of telomeric repeats during the repair of double-stranded DNA breaks via non-homologous end-joining (NHEJ) (Azzalin et al., 2001; Nergadze et al., 2004), possibly involving telomerase (Nergadze et al., 2007). Like many other microsatellites, s-ITSs are polymorphic in length (Hastie and Allshire, 1989); for instance, their significant length polymorphism has been observed in gastric tumors (Mondello et al., 2000). Cytogenetic analysis has co-localized ITSs with spontaneous and induced chromosome breakage sites in primates (Ruiz-Herrera et al., 2005) and rodents (Musio et al., 1996).
Telomeric repeats located within chromosomes are called interstitial telomeric sequences (ITSs). They are polymorphic in length and are likely hotspots for initiation of chromosomal rearrangements that have been linked to human disease. Using our S. cerevisiae system to study repeat-mediated genome instability, we have previously shown that yeast telomeric (Ytel) repeats induce various gross chromosomal rearrangements (GCR) when their G-rich strands serve as the lagging strand template for replication (G orientation). Here, we show that interstitial Ytel repeats in the opposite C orientation prefer to expand rather than cause GCR. A tract of eight Ytel repeats expands at a rate of 4 × 10⁻⁴ per replication, ranking them among the most expansion-prone DNA microsatellites. A candidate-based genetic analysis implicates both post-replication repair and homologous recombination pathways in the expansion process. We propose a model for Ytel repeat expansions and discuss its applications for genome instability and alternative telomere lengthening (ALT).
Effect of bleomycin on interstitial telomeric sequences of immortalized Chinese hamster ovary cells
2009, Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
The effect of the radiomimetic compound bleomycin (BLM) on interstitial telomeric sequences (ITSs) was investigated in Chinese hamster ovary (CHO) cells by using PNA-FISH with a pantelomeric probe. CHO cells were exposed to increasing concentrations of BLM and chromosomal aberrations were analyzed in the first mitosis after treatment. Cytogenetic analysis revealed that 18.1% and 9.5% of the total aberrations observed in cells exposed to BLM and harvested 18 h and 3 h after treatment, respectively, exhibited one or more FISH-detectable telomeric signals. Most of the chromosome breaks exhibiting telomeric signals observed in BLM-treated cells occurred in the centromeric regions of chromosomes. This observation, along with the finding of entirely labeled acentric fragments in BLM-exposed cells but not in untreated cells, shows that this antibiotic induces breakage at chromosomal sites containing ITSs. In addition, our results show that heterochromatic ITSs are involved more than expected in the formation of chromosome/chromatid breaks – and perhaps chromatid exchanges – induced by BLM, taking into account the percentage of the genome covered by telomeric sequences. On the contrary, our data strongly suggest that ITSs are not preferentially involved in the formation of dicentrics, multicentrics, centric rings, acentric fragments or chromatid deletions induced by BLM. Moreover, our results show that BLM is capable of inducing amplification and translocation of telomeric repeats, and suggest that this antibiotic produces breakage within centromeric ITSs, although chromosome regions containing these sequences are not the preferential target for BLM clastogenic action. On the other hand, our results show that BLM treatment increases the size of ITSs and that this effect is not related to the chromosomal sensitivity of the exposed cells to this compound.
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^∗: R.C. Allshire is now at Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, NY 11724, USA.

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Trends in Genetics

Human telomeres: fusion and interstitial sites

Abstract

Cell

Cell

Cell

Cancer Genet. Cytogenet.

Cell

Cell

Yeast

Nucleic Acids Res.

Mol. Cell. Biol.

Cell

Nature

Nature

Nature

Mol. Cell. Biol.

Nature

Nucleic Acids Res.

Nature

Nature

Nature