3 Roles of Transcription Factors in DNA

Sequence-specific recognition of DNA by proteins is essential for both transcription and DNA replication. Transcription factors form a growing family of regulatory proteins that can positively or negatively influence transcription by binding to regulatory elements in DNA contacting components of the basal transcription machinery. In recent years, it has become clear that several transcription factors are multifunctional and also directly influence initiation of DNA replication. This was first detected during studies of the replication of eukaryotic viruses, such as adenovirus and papovaviruses, but it may well be a more general phenomenon. Many viril origins consist of a core origin and auxiliary regions that contribute to the initiation of replication and are required for optimal viral growth (for review, see DePamphilis 1988, 1993a; Challberg and Kelly 1989; Stillman 1989). These auxiliary regions contain transcription factor-binding sites. In polyomavirus, presence of the transcriptional enhancer stimulated DNA replication up to lOOO-fold, and presence of the enhancer increased SV40 replication approximately 100-fold. The auxiliary region of adenovirus stimulates initiation of replication up to 200fold, although this region is not directly involved in transcription. The transcription factors used for enhancement of replication can be cellular as well as viral. Cellular transcription factors are involved in adenovirus, SV40, and polyomavirus replication. For papillomavirus and EpsteinBarr virus, the viral proteins (BPV-E2, EBNA1) combine functions in transcription and replication, as is the case for T antigen of SV40 and pol yomavirus. The availability of initiation systems that can be reconstituted with purified proteins for adenovirus and papovaviruses, combined with effi-