Studies on the Initiation of DNA Synthesis in Plant and Animal Cells

Abstract

DNA dependent DNA polymerases (E. C. 2. 7. 7. 7) play a key role in DNA replication by copying with high efficiency and fidelity the appropriate templates. These enzymes are, however, unable to initiate DNA synthesis in the absence of a primer able to provide a free 3’OH starting point (1). Several mechanisms have been described concerning the initiation of DNA synthesis by DNA polymerases. In Figure 1 we show schematically the different possibilities a DNA polymerase can find to start a DNA chain. In normally replicating prokaryotic or eukaryotic cells, DNA synthesis is initiated from short RNA primers synthesized by a unique kind of RNA polymerase called DNA primase (1). Discontinuous DNA synthesis gives raise to the so called Okazaki fragments which are then joined to give the high molecular weight nascent DNA. A very different mechanism is observed in the case of the replication of adenovirus DNA. The adenovirus coded DNA polymerase initiates DNA synthesis from a dCMP residue covalently linked to a 55 Kd protein (see van der Vliet et al., this volume). Parvovirus contain a single stranded DNA genome with a high degree of self complementarity; hairpin structures allow the initiation of DNA synthesis in this system by a cell coded DNA polymerase (see Vos et al., this volume).