Human telomeric 6; 19 translocation chromosome with a tendency to break at the fusion point

Drets, Máximo E.; Therman, Eeva

doi:10.1007/bf00327334

Cited by 34 publications

(12 citation statements)

References 16 publications

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“…ITS could also derive from the internalization of telomeres which have lost their function of protecting the end of the chromosome allowing them to be involved in rearrangements and thus becoming interstitial (Park et al, 1992;Rossi et al, 1993;Vermeesch et al, 1997). Such ITS have been reported to enhance chromosome breakages (Drets and Therman, 1983) and to be associated with high rates of chromosome rearrangements (Katinka and Bourgain, 1992;Bertoni et al, 1994). These data strengthen the idea that ITS are hot spots for recombination (Hastie and Allshire, 1989).…”

supporting

confidence: 74%

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

Desmaze

Alberti²,

Martins³

et al. 1999

Cytogenet Genome Res

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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.

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supporting

confidence: 74%

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

Desmaze

Alberti²,

Martins³

et al. 1999

Cytogenet Genome Res

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“…Consistent with this possibility are the observations that telomere repeat sequences are polymorphous (44) and have extremely high rates of gene conversion (48). Furthermore, a human chromosome translocation involving a telomeric region has been shown to break at the fusion point (11). The addition of telomere repeat sequences to DNA strand breaks by either recombination or telomerase could therefore explain the facts that gene amplification is greatly enhanced after chromosome fragmentation (14) and by rearrangements that place genes near the ends of chromosomes (43,46).…”

Section: Resultsmentioning

confidence: 81%

Acquisition of telomere repeat sequences by transfected DNA integrated at the site of a chromosome break.

Murnane

1993

Mol. Cell. Biol.

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Previous analysis of plasmid DNA transfected into 108 cell clones demonstrated extensive polymorphism near the integration site in one clone. This polymorphism was apparent by Southern blot analysis as diffuse bands that extended over 30 kb. In the present study, nucleotide sequence analysis of cloned DNA from the integration site revealed telomere repeat sequences at the ends of the integrated plasmid DNA. The telomere repeat sequences at one end were located at the junction between the plasmid and cell DNA. The telomere repeat sequences at the other end were located in the opposite orientation in the polymorphic region and were shown by digestion with BAL 31 to be at the end of the chromosome. Telomere repeat sequences were not found at this location in the plasmid or parent cell DNA. Although the repeat sequences may have been acquired by recombination, a more likely explanation is that they were added to the ends of the plasmid by telomerase before integration. Comparison of the cell DNA before and after integration revealed that a chromosome break had occurred at the integration site, which was shown by fluorescent in situ hybridization to be located near the telomere of chromosome 13. These results demonstrate that chromosome breakage and rearrangement can result in interstitial telomere repeat sequences within the human genome. These sequences could promote genomic instability, because short repeat sequences can be recombinational hotspots. The results also show that

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“…Hastie and Allshire (35) have cited several features of a putative telomere-telomere fusion that make it an attractive candidate for the fragile site in this band. In the sole example of a constitutional telomere-telomere fusion in human, a high rate of chromosome gaps and breaks was reported at the fusion point between chromosomes 6 and 19, although the presence of residual telomere repeats at the fusion point was not confirmed (36).…”

Section: Identiflication and Characterization Of Genomic Cosmidsmentioning

confidence: 99%

Origin of human chromosome 2: an ancestral telomere-telomere fusion.

IJdo

Baldini

Ward

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

337

236

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We have identified two allelic genomic cosmids from human chromosome 2, c8.1 and c29B, each containing two inverted arrays of the vertebrate telomeric repeat in a head-to-head arrangement, 5'(TTAGGG),,-(CCCTAA),,3'. Sequences fln g this telomeric repeat are characteristic of present-day human pretelomeres. BAL-31 nuclease experiments with yeast artificial chromosome clones of human telomeres and fluorescence in situ hybridization reveal that sequences flanking these inverted repeats hybridize both to band 2q13 and to different, but overlapping, subsets of human chromosome ends. We conclude that the locus cloned in cosmids c8.1 and c29B is the relic of an ancient telomeretelomere fusion and marks the point at which two ancestral ape chromosomes fused to give rise to human chromosome 2.Similarities in chromosome banding patterns and hybridization homologies between ape and human chromosomes suggest that human chromosome 2 arose out of the fusion of two ancestral ape chromosomes (1-3). Molecular data show evidence that this event must have occurred only a few million years ago (refs. 4 and 5 and the references therein). Although the precise nature of this putative fusion is unknown, cytogenetic data point to either a centromeric or telomeric fusion in the vicinity of region 2ql (1, 2, and 6). The observation that telomeric DNA is present in chromosomal band q13 suggests that telomeres, the extreme ends of chromosomes, may have been involved in this fusion (7,8). Normally, telomeres form a dynamic buffer against loss of internal sequence and prevent chromosomes from fusing (for review, see ref. 9). By contrast, nontelomeric DNA ends are subject to degradation by nucleases and to fusion by ligation (10,11).The termini of human chromosomes consist of head-to-tail tandem arrays ofTTAGGG, running 5'--3' toward the end of the chromosome, with average lengths of 5-10 kilobases (kb) in somatic cells (7,12,13). The proximal ends of these arrays contain degenerate forms of this repeat, such as (TTGGGG), and (TGAGGG)J, (14). Sequences adjacent to these simple repeats have been characterized in a number of human chromosomes and shown to consist of repetitive elements, each shared by a subset of all chromosomes (13,(15)(16)(17). In addition, stretches of telomeric repeats are present at interstitial sites, usually in subtelomeric regions but also at a distinct internal site within band 2q13 (8). We describe here the architecture of the sequence at this internal locus at 2q13, which represents a relic of the fusion of two ancestral ape chromosomes in the evolution ofhuman chromosome 2. 11 MATERIALS AND METHODS Library Screening. Approximately 1.4 x 106 colonies from a human genomic cosmid library containing Mbo I partial digestion fragments of 35-41 kb in vector pWE15, propagated in host NM554 (Stratagene), were screened with pSC4, a human genomic 300-base-pair (bp) Alu I fragment present at the subtelomeric regions offive different chromosomes, as well as at a single nonterminal locus at 2q13, described elsewhere (8). ...

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Human telomeric 6; 19 translocation chromosome with a tendency to break at the fusion point

Cited by 34 publications

References 16 publications

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

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

Acquisition of telomere repeat sequences by transfected DNA integrated at the site of a chromosome break.

Origin of human chromosome 2: an ancestral telomere-telomere fusion.

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