title: Telomere sequences at the novel joints of four independent amplifications in Saccharomyces cerevisiae.
abstract: Primary gene amplification, the mutation from one copy of a gene per genome to two or more genes per genome is a major mechanism of oncogene overexpression. We previously developed a system in the yeast Saccharomyces cerevisiae to phenotypically detect primary amplifications of a reporter cassette, ADH4:CUP1. We present here the sequence analysis of novel joints from four independent, spontaneous circular amplifications identified by the ADH4:CUP1 system. All four novel joints consist of C(1-3) A telomeric repeats joined to short (14- to 16-bp) CA-rich tracts between ADH4 and the telomere of chromosome VII. In three of the four amplifications, the telomeric sequence and the CA-rich tract that are joined in the amplification are normally located in inverted orientation to each other on chromosome VII. In the fourth amplification, the CA-rich tract on chromosome VII is joined to telomere sequences from another chromosome. We suggest that formation of these amplifications was initiated by recombination between these CA-rich tracts and a telomere. The resulting dicentric chromosome could start a breakage-fusion-bridge cycle that could be resolved by the formation of a circular amplification structure.
authors.affiliation: Yale University, New Haven, Connecticut, USA.
authors.forename: I K
authors.initials: IK
authors.lastname: Moore
authors.forename: M P
authors.initials: MP
authors.lastname: Martin
authors.forename: C E
authors.initials: CE
authors.lastname: Paquin
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins; D003001:Cloning, Molecular; D005784:Gene Amplification; D017930:Genes, Reporter; D008668:Metallothionein / Q000235:genetics; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016615:Telomere / Q000235:genetics*
chemical_list: C500769:CUP1-1 protein, S cerevisiae; D002352:Carrier Proteins; C007121:copper thionein; D008668:Metallothionein