An in vitro and in vivo study of a BrdU-sensitive fragile site in the Chinese hamster

Lin, MC; Takabayashi, T.; Wilson, M; Marchese, Cristiana

doi:10.1159/000132062

Cited by 21 publications

(13 citation statements)

References 3 publications

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“…Serially cultured cells have been reported to sponta neously evolve toward transformation and to acquire a modal chromosomal number with many rearranged chromosomes typical of each cell line (Worton et al, 1977;Simi et al, 1992). Chromosome rearrangements are also produced by exogenous factors, such as 5-bromodeoxyuridine (BrdU) and methotrex ate, and have been shown to preferentially involve bands that have been mapped as fragile sites (Lin et al, 1984;Simi et al, 1990).…”

mentioning

confidence: 99%

Spontaneous and aphidicolin-sensitive fragile site 3cen co-localizes with the (TTAGGG)<sub>n</sub> telomeric sequence in Chinese hamster cells

Musio

Rainaldi²,

Sbrana³

1996

Cytogenet Genome Res

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Aphidicolin-sensitive fragile sites were analyzed in immortalized Chinese hamster embryonal fibroblast cells (CHEF 18) at three different passages along their spontaneous progression toward tumorigenicity. Five fragile sites (viz., 1q22, 3cen, 3p21, 3q31, and Xq21) were detected. Three of these sites carry spontaneous aberrations and are thus regions of chromosomal instability; however, they were not involved in the formation of the clonal rearrangements that are characteristic of CHEF 18 cells. The presence of the (TTAGGG)_n telomeric sequence in chromosome bands associated with fragile sites was investigated using fluorescence in situ hybridization and primed in situ labeling. A common location of fragile sites and telomeric sequence was found at the centromere of chromosome 3.

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mentioning

confidence: 99%

Spontaneous and aphidicolin-sensitive fragile site 3cen co-localizes with the (TTAGGG)<sub>n</sub> telomeric sequence in Chinese hamster cells

Musio

Rainaldi²,

Sbrana³

1996

Cytogenet Genome Res

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“…In the Chinese hamster there is a BrdU inducible fragile site at lq22 which can be demonstrated in vitro and in vivo (Lin et al 1984). Likewise, a potential BrdU sensitive fragile site has been reported in the cactus mouse, Peromyscus eremicus (Schneider et al 1980).…”

Section: Common Fragile Sitesmentioning

confidence: 85%

Report of the committee on cytogenetic markers

Sutherland¹,

Ledbetter²

1988

Cytogenet Genome Res

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“…Fragile sites have been reported in mouse, rat, hamster, cow, cat, and dog (35)(36)(37)(38)(39)(40). They appear to be inherent and universal structures of the mammalian genome.…”

Section: Discussionmentioning

confidence: 99%

Sequence conservation at human and mouse orthologous common fragile regions, FRA3B / FHIT and Fra14A2 / Fhit

Shiraishi

Druck

Mimori

et al. 2001

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

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It has been suggested that delayed DNA replication underlies fragility at common human fragile sites, but specific sequences responsible for expression of these inducible fragile sites have not been identified. One approach to identify such cis-acting sequences within the large nonexonic regions of fragile sites would be to identify conserved functional elements within orthologous fragile sites by interspecies sequence comparison. This study describes a comparison of orthologous fragile regions, the human FRA3B͞FHIT and the murine Fra14A2͞Fhit locus. We sequenced over 600 kbp of the mouse Fra14A2, covering the region orthologous to the fragile epicenter of FRA3B, and determined the Fhit deletion break points in a mouse kidney cancer cell line (RENCA). The murine Fra14A2 locus, like the human FRA3B, was characterized by a high AT content. Alignment of the two sequences showed that this fragile region was stable in evolution despite its susceptibility to mitotic recombination on inhibition of DNA replication. There were also several unusual highly conserved regions (HCRs). The positions of predicted matrix attachment regions (MARs), possibly related to replication origins, were not conserved. Of known fragile region landmarks, five cancer cell break points, one viral integration site, and one aphidicolin break cluster were located within or near HCRs. Thus, comparison of orthologous fragile regions has identified highly conserved sequences with possible functional roles in maintenance of fragility.C haracterization and sequencing of inherited fragile sites have determined the specific cause of fragility at a number of rare fragile sites; for example, FRA11B is caused by expansion of CGG triplets and FRA16B by AT rich minisatellite repeats (1, 2). These rare fragile sites were isolated by positional cloning of the relevant genomic loci from DNA of family members segregating these rare fragile sites. However, the common non-familial fragile sites (n Ͻ 100) are considered to be normal chromosome structures. To date, common fragile sites FRA3B (3), FRA7H (4), FRA7G (5), and FRA16D (6, 7) have been identified, cloned, and sequenced. Analyses and comparisons of these sequences have not revealed the mechanism of their fragility, although they revealed that common fragile sites are actually large fragile regions (Ϸ150 to 1,000 kbp). Expanded repeats were not found in these fragile regions (4,8,9).The human FRA3B locus at chromosome region 3p14.2 is the most inducible common fragile site, exhibiting apparent breaks in up to 50% of metaphases after exposure to aphidicolin (10). Deletions and structural rearrangements in FRA3B have been observed in a large fraction of tumor types. The tumor suppresser gene FHIT encompasses the FRA3B fragile region and is altered by deletion or translocation in many types of cancer, including those of lung, cervix, esophagus, bladder, and kidney carcinomas (11-16). We have been interested in the mechanism of fragility in this region and its contribution to cancer susceptibility. Previously, w...

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An in vitro and in vivo study of a BrdU-sensitive fragile site in the Chinese hamster

Cited by 21 publications

References 3 publications

Spontaneous and aphidicolin-sensitive fragile site 3cen co-localizes with the (TTAGGG)<sub>n</sub> telomeric sequence in Chinese hamster cells

Spontaneous and aphidicolin-sensitive fragile site 3cen co-localizes with the (TTAGGG)<sub>n</sub> telomeric sequence in Chinese hamster cells

Report of the committee on cytogenetic markers

Sequence conservation at human and mouse orthologous common fragile regions, FRA3B / FHIT and Fra14A2 / Fhit

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