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Uncoupling the replication machinery: Replication fork progression in the absence of processive DNA synthesis

Item Type:Article
Title:Uncoupling the replication machinery: Replication fork progression in the absence of processive DNA synthesis
Creators Name:Goerisch, S.M. and Sporbert, A. and Stear, J.H. and Grunewald, I. and Nowak, D. and Warbrick, E. and Leonhardt, H. and Cardoso, M.C.
Abstract: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.
Keywords:PCNA, DNA Polymerase, RPA, DNA Ligase I, Fen1, Mcm, Replication Machinery, Aphidicolin, Animals, Mice
Source:Cell Cycle
ISSN:1538-4101
Publisher:Landes Bioscience (U.S.A.)
Volume:7
Number:13
Page Range:1983-1990
Date:1 July 2008
Official Publication:https://doi.org/10.4161/cc.7.13.6094
PubMed:View item in PubMed

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