Transcription Enhances Intrachromosomal Homologous Recombination in Mammalian Cells

The influence of transcription on homologous intrachromosomal recombination between direct and inverted repeats has been examined by using Chinese hamster ovary cells. Recombination was monitored between two integrated neomycin (neo) genes, including one silent allele and a second allele regulated by the inducible mouse mammary tumor virus promoter. Transcription of mouse mammary tumor virus neo alleles was regulated with the glucocorticoid hormone dexamethasone. Alleles transcribed at high levels recombined about two- to sevenfold more frequently than identical alleles transcribed at low levels. Direct repeats recombined primarily by a gene conversion mechanism; inverted repeats produced a variety of rearranged products. These results are discussed in relation to recombinational processes that regulate gene expression, influence gene family structures, and mediate genomic instability associated with cellular transformation and tumorigenesis.