A model for the formation of the duplicated enhancers found in polyomavirus regulatory regions.

When purified from persistent infections, the genomes of most human polyomaviruses contain single enhancers. However, when isolated from productively infected cells from immunocompromised individuals, the genomes of several polyomaviruses contain duplicated enhancers that promote a number of polyoma-based diseases. The mechanism(s) that gives rise to the duplicated enhancers in the polyomaviruses is, however, not known. Herein we propose a model for the duplication of the enhancers that is based on recent advances in our understanding of; 1) the initiation of polyomavirus DNA replication, 2) the formation of long flaps via displacement synthesis and 3) the subsequent generation of duplicated enhancers via double stranded break repair. Finally, we discuss the possibility that the polyomavirus based replication dependent enhancer duplication model may be relevant to the enhancer-associated rearrangements detected in human genomes that are associated with various diseases, including cancers.