Telomeric and Nontelomeric (TTAGGG)n Sequences in Gene Amplification and Chromosome Stability

Bertoni, Livia; Attolini, Carmen; Tessera, L.; Mucciolo, Elena; Giulotto, Elena

doi:10.1006/geno.1994.1581

Cited by 86 publications

(62 citation statements)

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“…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.…”

Section: Discussionsupporting

confidence: 77%

Insertion of Telomeric Repeats at Intrachromosomal Break Sites During Primate Evolution

Nergadze

Rocchi²,

Azzalin³

et al. 2004

Genome Res.

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108

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Short blocks of telomeric-like DNA (Interstitial Telomeric Sequences, ITSs) are found far from chromosome ends. We addressed the question as to how such sequences arise by comparing the loci of 10 human ITSs with their genomic orthologs in 12 primate species. The ITSs did not derive from expansion of pre-existing TTAGGG units, as described for other microsatellites, but appeared suddenly during evolution. Nine insertion events were dated along the primate evolutionary tree, the dates ranging between 40 and 6 million years ago. Sequence comparisons suggest that in each case the block of (TTAGGG) n DNA arose as a result of double-strand break repair. In fact, ancestral sequences were either interrupted precisely by the tract of telomeric-like repeats or showed the typical modifications observed at double-strand break repair sites such as short deletions, addition of random sequences, or duplications. Similar conclusions were drawn from the analysis of a chimpanzee-specific ITS. We propose that telomeric sequences were inserted by the capture of a telomeric DNA fragment at the break site or by the telomerase enzyme. Our conclusions indicate that human ITSs are relics of ancient breakage rather than fragile sites themselves, as previously suggested.

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Section: Discussionsupporting

confidence: 77%

Insertion of Telomeric Repeats at Intrachromosomal Break Sites During Primate Evolution

Nergadze

Rocchi²,

Azzalin³

et al. 2004

Genome Res.

Self Cite

108

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“…The presence of free ends of chromosomes following exposure to DNA-damaging agents facilitates telomerase to use them as primers for the addition of telomeric repeats both in vivo and in vitro (Flint et al, 1994). New telomeres may be seeded following breakage within the intrachromosomal telomeric repeats to stabilize the rearranged chromosomes (Bertoni et al, 1994). As there was a dose dependent increase in telomerase activity, it is likely that the extent of DNA damage might trigger the telomerase activity and the UV-doses used in the present experiment are high enough to induce su cient amounts of breakage events.…”

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confidence: 89%

Induction of telomerase activity by UV-irradiation in Chinese hamster cells

1997

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Telomerase is a ribonucleoprotein whose activity has been detected in germline cells and in neoplastic and immortal cells. Telomerase compensates the telomere loss arising by the end replication problem by synthesizing telomeric repeats at the 3' end of the eukaryotic chromosomes. Telomerase is reactivated during cancer progression in human and mice. In order to determine whether the telomerase activity can be upregulated in vitro in response to DNA damaging agents, we examined the telomerase activity in ®ve Chinese hamster cell lines following exposure to 5 J/m 2 or 40 J/m 2 UV-C radiation. All the cell lines tested showed an increase in telomerase activity in the PCRbased telomeric repeat ampli®cation protocol (TRAP) in a dose dependent manner. This increase in telomerase activity correlated well with the number of cells being in the S and G 2 /M phase after UV exposure. However, in unirradiated control cells, similar levels of telomerase activity were observed in di erent phases of the cell cycle. Furthermore, telomeric signals were clustered in one or more parts of the disintegrating nuclear particles of the apoptotic cell as detected by¯uorescence in situ hybridization (FISH). This is the ®rst study to demonstrate the induction of telomerase activity following exposure to DNA-damaging agents like UV radiation in Chinese hamster cells in vitro.

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“…It has also been suggested that interstitial telomeric sequences are sites of preferential chromosome breakage, amplification, and recombination (Bertoni et al 1994;Boutouil et al 1996;Slijepcevic et al 1996;Simi et al 1998;Desmaze et al 1999). Some internal telomeric repeats map at cytogenetic resolution together with mapped fragile sites (Musio and Mariani 1999).…”

Section: Paralogy and (Deleterious) Rearrangementsmentioning

confidence: 99%

Genomic Structure and Evolution of the Ancestral Chromosome Fusion Site in 2q13–2q14.1 and Paralogous Regions on Other Human Chromosomes

Fan

Linardopoulou²,

Friedman³

et al. 2002

Genome Res.

111

100

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Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13-2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%-99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ∼100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans.

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Telomeric and Nontelomeric (TTAGGG)n Sequences in Gene Amplification and Chromosome Stability

Cited by 86 publications

References 0 publications

Insertion of Telomeric Repeats at Intrachromosomal Break Sites During Primate Evolution

Insertion of Telomeric Repeats at Intrachromosomal Break Sites During Primate Evolution

Induction of telomerase activity by UV-irradiation in Chinese hamster cells

Genomic Structure and Evolution of the Ancestral Chromosome Fusion Site in 2q13–2q14.1 and Paralogous Regions on Other Human Chromosomes

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