Formation of an Inverted Duplication Can Be an Initial Step in Gene Amplification

• DOI: 10.1128/mcb.8.10.4302-4313.1988
• Publication Date: 2021-05-28T14:33:20Z
• Authors: Joseph C. Ruiz; Geoffrey M. Wahl
• Keywords: Extrachromosomal DNA; Gene dosage; Inverted repeat

We have developed a gene transfer approach to facilitate the identification and isolation of chromosomal regions which are prone high-frequency amplification. Such identified by assaying for transformants show resistance PALA and/or methotrexate amplification vector containing genes encode enzyme targets these antiproliferative agents. 2 47 displayed transfected genes, in this report we describe analysis one them (L46). Molecular integration site transformant L46 revealed that donated were at center an inverted duplication spanned more than 70 kilobase pairs consisted largely host DNA. The data suggest sequences generates submicroscopic molecule least 750 kilobases additional sequences. readily amplified lost exponentially growing cultures absence drug selection, suggests extrachromosomal elements acentric. In contrast instability region following insertion, preinsertion was maintained single copy level under growth conditions produced number heterogeneity L46. implications our results mechanisms genetic mammalian discussed.