Uncoupling the replication machinery: Replication fork progression in the absence of processive DNA synthesis
| Autor: | Sabine M. Görisch, Ingrid Grunewald, Emma Warbrick, Danny Nowak, Anje Sporbert, Heinrich Leonhardt, Jeffrey H. Stear, M. Cristina Cardoso |
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| Rok vydání: | 2008 |
| Předmět: |
DNA Replication
DNA Ligases Semiconservative replication Eukaryotic DNA replication DNA-Directed DNA Polymerase Biology Cell Line Myoblasts DNA replication factor CDT1 DNA Ligase ATP Mice Replication factor C Aphidicolin Minichromosome maintenance Control of chromosome duplication Proliferating Cell Nuclear Antigen Animals Humans Enzyme Inhibitors Molecular Biology DNA replication DNA Cell Biology Molecular biology Cell biology DNA-Binding Proteins Repressor Proteins biology.protein Origin recognition complex HeLa Cells Developmental Biology |
| Zdroj: | Cell Cycle. 7:1983-1990 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.7.13.6094 |
| Popis: | The precise coordination of the different steps of DNA replication is critical for the maintenance of genome stability. We have probed the mechanisms coupling various components of the replication machinery and their response to polymerase stalling by inhibition of the DNA polymerases in living mammalian cells with aphidicolin. We observed little change in the behaviour of proteins involved in the initiation of DNA replication. In contrast, we detected a marked accumulation of the single stranded DNA binding factor RPA34 at sites of DNA replication. Finally, we demonstrate that proteins involved in the elongation step of DNA synthesis dissociate from replication foci in the presence of aphidicolin. Taken together, these data indicate that inhibition of processive DNA polymerases uncouples the initiation of DNA replication from subsequent elongation steps. We, therefore, propose that the replication machinery is made up of distinct functional sub-modules that allow a flexible and dynamic response to challenges during DNA replication. |
| Databáze: | OpenAIRE |
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