title: Gene amplification system based on double rolling-circle replication as a model for oncogene-type amplification.
abstract: Gene amplification contributes to a variety of biological phenomena, including malignant progression and drug resistance. However, details of the molecular mechanisms remain to be determined. Here, we have developed a gene amplification system in yeast and mammalian cells that is based on double rolling-circle replication (DRCR). Cre-lox system is used to efficiently induce DRCR utilizing a recombinational process coupled with replication. This system shows distinctive features seen in amplification of oncogenes and drug-resistance genes: (i) intra- and extrachromosomal amplification, (ii) intensive chromosome rearrangement and (iii) scattered-type amplification resembling those seen in cancer cells. This system can serve as a model for amplification of oncogenes and drug-resistance genes, and improve amplification systems used for making pharmaceutical proteins in mammalian cells.
authors.affiliation: National Institute for Basic Biology, Department of Basic Biology, The Graduate University for Advanced Studies (Sokendai), Myodaiji, Okazaki, Aichi, 444-8585, Japan. watatka@nibb.ac.jp
authors.forename: Takaaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tanabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Horiuchi
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication; D005784:Gene Amplification; D019426:Integrases / Q000378:metabolism; D008957:Models, Genetic; D009857:Oncogenes; D011995:Recombination, Genetic; D015003:Yeasts / Q000235:genetics
chemical_list: C045073:Cre recombinase; D019426:Integrases