COMMENTARY DNA polymerase d/PCNA: actions and interactions

Recent work has shown that the proliferating cell nuclear antigen (PCNA) is an essential component for the replication of the eucaryotic virus, SV40, in a human cell extract. This is due to its interaction with a hitherto overlooked DNA polymerase (pol <5), and this discovery has brought these two proteins under the scrutiny of those working in the cell cycle, replication and DNA polymerase fields. However, there has been some confusion in the literature surrounding the description of these two important proteins. Through the years PCNA has been independently described as three separate proteins, namely PCNA, cyclin and the DNA polymerase 6 auxiliary protein (see below). To add to the confusion, a totally distinct protein, which was identified in fertilised sea-urchin and clam eggs (Evans et al. 1983), was also called 'cyclin'. This cyclin bears no relation to the protein described here. If this were not enough, as soon as opinion appeared to agree that pol 5 was in fact a separate enzyme and not a derivative of pol a as had been suggested (one of the distinguishing criteria being that the mode of action of pol <5 was dramatically affected by PCNA), then several groups began to find two types of pol 8. Both of these exhibited '<5-like' properties but differed in their ability to respond to the auxiliary factor. The aim of this article is to clarify this picture, first by describing pol <5 and how this enzyme differs from pol a, and also by briefly reviewing the history of PCNA, especially in its relation to pol 6. In conclusion I would like to suggest how the two different types of pol <5, one PCNA-dependent and the other PCNA-independent, may have different functions in eucaryotic cells.