Figure 1.

Adozelesin inhibits initiation of mammalian chromosomal DNA replication. (A) K562 and MDA cells were treated with 40 nM adozelesin for indicated times and DNA synthesis was assessed by measuring tritiated thymidine incorporation into acid-precipitable DNA. (B) K562 cells were treated with indicated concentrations of adozelesin for 2 h and DNA synthesis was assessed as in A. (C) Replicating and nonreplicating DNA isolated from K562 cells treated with adozelesin or adozelesin + aphidicolin (aph) for the indicated times were separated from one another by neutral-neutral two-dimensional gel electrophoresis, and blots of gels were probed with a fragment of DNA from the tandemly repeated human rDNA locus. Schematic shows migration of single branched replication intermediates and nonreplicating DNA molecules (1N DNA).