The step in cellular DNA synthesis blocked by Newcastle disease or mengovirus infection

Abstract

Infection of L cells with Newcastle disease or mengovirus results in rapid inhibition of cellular protein and DNA synthesis. Sedimentation analyses indicate that high molecular weight cellular DNA is not degraded during infection with either virus even when DNA synthesis is 90% inhibited; nor are the activities of enzymes essential for DNA synthesis significantly reduced in extracts of infected cells. Sedimentation analyses in alkaline gradients show that nascent DNA chains grow with normal kinetics under conditions where overall DNA synthesis is inhibited by viral infection. Inhibition of DNA synthesis during viral infection probably reflects reduced numbers of chromosomal regions active in replication rather than reduced rates of polymerization within such regions. Treatment of cells with chemical inhibitors of protein synthesis has an effect similar to viral infection in that DNA chain elongation occurs normally although apparently the number of actively replicating chromosomal regions is reduced. Earlier and present results are compatible with the view that initiation of DNA synthesis upon regulatory units of DNA replication is the step in DNA synthesis that requires concurrent protein synthesis. Viral inhibition of cellular protein synthesis may thus be the primary insult which in turn affects adversely the initiation of DNA synthesis.