title: [Gene amplification and chromosomal rearrangements during acquisition of cellular resistance to the antimetabolite coformycin].
abstract: We studied the early stages of gene amplification in a Chinese hamster cell line and we show that two distinct mechanisms can operate at a single locus. Both of them rely on an unequal segregation of gene copies at mitosis. We conclude that cycles of chromatid breakage, followed by fusion of sister chromatids devoid of a telomere that lead to further breaks in mitosis, have a key role in the coupling of gene amplification and genome remodeling. Rearrangements are first limited to a single chromosome but can then potentially spread to any additional chromosome. Occasionally, a sequence containing the selected gene can be looped out, generating a "double minute" and thus initiating an independent process of extrachromosomal amplification.
authors.affiliation: Unité de génétique somatique (URA CNRS 361), Institut Pasteur, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Debatisse
authors.forename: F
authors.initials: F
authors.lastname: Toledo
authors.forename: G
authors.initials: G
authors.lastname: Buttin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000235:genetics*; D002999:Clone Cells; D003070:Coformycin / Q000494:pharmacology*; D006224:Cricetinae; D004351:Drug Resistance; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects; D005784:Gene Amplification / Q000187:drug effects / Q000235:genetics*; D015321:Gene Rearrangement; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D007621:Karyotyping; D012854:Sister Chromatid Exchange / Q000235:genetics
chemical_list: D003070:Coformycin
vernacular_title: Amplification génique et réarrangements chromosomiques lors de l'acquisition de la résistance cellulaire à un antimétabolite, la coformycine.