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

Görisch, Sabine M. and Sporbert, Anje and Stear, Jeffrey H. and Grunewald, Ingrid and Nowak, Danny and Warbrick, Emma and Leonhardt, Heinrich and Cardoso, M Cristina (2008):
Uncoupling the replication machinery: replication fork progression in the absence of processive DNA synthesis.
In: Cell cycle (Georgetown, Tex.), pp. 1983-90, 7, (13), ISSN 1551-4005, [Online-Edition: http://www.cardoso-lab.org/publications/Gorisch_2008.pdf],
[Article]

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.

Item Type: Article
Erschienen: 2008
Creators: Görisch, Sabine M. and Sporbert, Anje and Stear, Jeffrey H. and Grunewald, Ingrid and Nowak, Danny and Warbrick, Emma and Leonhardt, Heinrich and Cardoso, M Cristina
Title: Uncoupling the replication machinery: replication fork progression in the absence of processive DNA synthesis.
Language: English
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.

Journal or Publication Title: Cell cycle (Georgetown, Tex.)
Volume: 7
Number: 13
Divisions: 10 Department of Biology > Cell Biology and Epigenetics
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10 Department of Biology
Date Deposited: 06 Mar 2010 16:00
Official URL: http://www.cardoso-lab.org/publications/Gorisch_2008.pdf
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