Aphidicolin prevents mitotic cell division by interfering with the activity of DNA polymerase-α

Abstract

THE study of the control of DNA synthesis would be helped if a variety of chemicals which influenced DNA synthesis in various ways was available. We have searched for chemicals which prevent mitotic division of sea urchin embryos, which requires DNA synthesis, but do not prevent meiotic divisions of starfish oocytes, which are independent of DNA synthesis¹. Aphidicolin² (I) is one such compound. Furthermore, recent experiments have shown that aphidicolin selectively inhibits the activity of DNA polymerase-α obtained from regenerating rat liver without interfering with the activity of DNA polymerase-β and mitochondrial DNA polymerase³. The function of the DNA polymerases in the complex process of DNA replication is not known. Correlative studies of DNA synthesis and the level of DNA polymerase activity suggest that DNA polymerase-α may be important in DNA replication⁴. However, in certain cases, DNA polymerase-β and -γ also increase at the time of DNA synthesis, and attempts to specify which of the DNA polymerases is ‘replicative’ or to assign roles to the various polymerases have not yet been successful⁴. We report here evidence that prevention of cell division by aphidicolin in sea urchin embryos is due to selective inhibition of DNA polymerase-α activity. This study implies a functional role for this polymerase activity during replication of DNA.