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


Dahm, K; Hübscher, U (2002). Colocalization of human Rad17 and PCNA in late S phase of the cell cycle upon replication block. Oncogene, 21(50):7710-7719.

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.

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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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:05 Vetsuisse Faculty > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:31 October 2002
Deposited On:11 Feb 2008 12:18
Last Modified:05 Apr 2016 12:15
Publisher:Nature Publishing Group
ISSN:0950-9232
Publisher DOI:https://doi.org/10.1038/sj.onc.1205872
PubMed ID:12400013

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