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Colocalization of human Rad17 and PCNA in late S phase of the cell cycle upon replication block

Oncogene volume 21, pages 7710–7719 (2002)Cite this article

Abstract

In response to replication block or DNA damage in S phase the DNA replication and DNA damage checkpoints are activated. The current model in human predicts, that a Rad17/Replication factor C (RF-C) complex might serve as a recruitment complex for the Rad9/Hus1/Rad1 complex to sites of replication block or DNA damage. In this study we have investigated the fate of the Rad17/RF-C complex after treatment of synchronized Hela cells with the replication inhibitor hydroxyurea. In hydroxyurea treated cells the RF-C p37 subunit became more resistant to extraction. Moreover, co-immunoprecipitation studies with extracts of hydroxyurea treated cells showed an interaction of RF-C p37 with Rad17 and of PCNA with Rad9 and RF-C p37. An enhanced colocalization of Rad17 and PCNA in late S phase after hydroxyurea treatment was observed. Our data suggested, that upon replication block a Rad17/RF-C complex is recruited to sites of DNA lesions in late S phase, binds the Rad9/Hus1/Rad1 complex and enables it to interact with PCNA. An interaction of Rad17/RF-C with PCNA appears to be mediated by the small RF-C p37 subunit, suggesting that PCNA might provide communication between replication checkpoint control and DNA replication and repair.

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Acknowledgements

We thank S Keller for technical support and advice, S Koundrioukoff for help with cell culture and T Bächi, AG Bittermann and M Höchli for their support with confocal microscopy. We are indebted to M Foiani for his critical reading of the manuscript. This study was supported by the Swiss National Science Foundation (grant 3100. 061361. 00), by Cancer League of the Kanton Zürich and by the Kanton of Zürich.

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  1. Institute of Veterinary Biochemistry and Molecular Biology, University Zürich-Irchel, Winterthurerstrasse 190, Zürich, 8057, Switzerland

    Kirsten Dahm & Ulrich Hübscher

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Correspondence to Ulrich Hübscher.

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Dahm, K., Hübscher, U. Colocalization of human Rad17 and PCNA in late S phase of the cell cycle upon replication block. Oncogene 21, 7710–7719 (2002). https://doi.org/10.1038/sj.onc.1205872

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