1. Temporally coordinated assembly and disassembly of replication factories in the absence of DNA synthesis
- Author
-
David M. Gilbert and Daniela S. Dimitrova
- Subjects
DNA Replication ,Time Factors ,Replication Origin ,Eukaryotic DNA replication ,CHO Cells ,Biology ,Pre-replication complex ,Chromosomes ,Article ,S Phase ,Replication factor C ,Aphidicolin ,Minichromosome maintenance ,Control of chromosome duplication ,Caffeine ,Cricetinae ,Proliferating Cell Nuclear Antigen ,Replication Protein A ,Animals ,2-Aminopurine ,Protein Kinase Inhibitors ,Replication protein A ,DNA replication ,Nuclear Proteins ,Minichromosome Maintenance Complex Component 2 ,Cell Biology ,Chromatin ,Cell biology ,DNA-Binding Proteins ,Origin recognition complex - Abstract
Here we show that exposure of aphidicolin-arrested Chinese hamster ovary (CHO) cells to the protein-kinase inhibitors 2-aminopurine or caffeine results in initiation of replication at successively later-replicating chromosomal domains, loss of the capacity to synthesize DNA at earlier-replicating sites, release of Mcm2 proteins from chromatin, and redistribution of PCNA and RPA from early- to late-replicating domains in the absence of detectable elongation of replication forks. These results provide evidence that, under conditions of replicational stress, checkpoint controls not only prevent further initiation but may also be required to actively maintain the integrity of stalled replication complexes.
- Published
- 2000