Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr(506) by cyclin-dependent kinases regulates binding to PCNA

Replication factor C (RF-C) complex binds to DNA primers and loads PCNA onto DNA, thereby increasing the processivity of DNA polymerases. We have previously identified a distinct region, domain B, in the large subunit of human RF-C (RF-Cp145) which binds to PCNA. We show here that the functional int...

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Main Authors: Salles-Passador, Isabelle, Munshi, Anil, Cannella, Dominique, Pennaneach, Vincent, Koundrioukoff, Stephane, Jacquinod, Michel, Forest, Eric, Podust, Vladimir, Fotedar, Arun, Fotedar, Rati
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Idioma:en
Publicado em: Oxford University Press 2003
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Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC212794/
https://ncbi.nlm.nih.gov/pubmed/12930972
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/nar/gkg692
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spelling pubmed-2127942003-10-23 Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr(506) by cyclin-dependent kinases regulates binding to PCNA Salles-Passador, Isabelle Munshi, Anil Cannella, Dominique Pennaneach, Vincent Koundrioukoff, Stephane Jacquinod, Michel Forest, Eric Podust, Vladimir Fotedar, Arun Fotedar, Rati Nucleic Acids Res Articles Replication factor C (RF-C) complex binds to DNA primers and loads PCNA onto DNA, thereby increasing the processivity of DNA polymerases. We have previously identified a distinct region, domain B, in the large subunit of human RF-C (RF-Cp145) which binds to PCNA. We show here that the functional interaction of RF-Cp145 with PCNA is regulated by cdk-cyclin kinases. Phosphorylation of either RF-Cp145 as a part of the RF-C complex or RF-Cp145 domain B by cdk-cyclin kinases inhibits their ability to bind PCNA. A cdk-cyclin phosphorylation site, Thr(506) in RF-Cp145, identified by mass spectrometry, is also phosphorylated in vivo. A Thr(506)→Ala RF-Cp145 domain B mutant is a poor in vitro substrate for cdk-cyclin kinase and, consequently, the ability of this mutant to bind PCNA was not suppressed by phosphorylation. By generating an antibody directed against phospho-Thr(506) in RF-Cp145, we demonstrate that phosphorylation of endogenous RF-Cp145 at Thr(506) is mediated by CDKs since it is abolished by treatment of cells with the cdk-cyclin inhibitor roscovitine. We have thus mapped an in vivo cdk-cyclin phosphorylation site within the PCNA binding domain of RF-Cp145. Oxford University Press 2003-09-01 /pmc/articles/PMC212794/ /pubmed/12930972 http://dx.doi.org/10.1093/nar/gkg692 Text en Copyright © 2003 Oxford University Press
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Articles
spellingShingle Articles
Salles-Passador, Isabelle
Munshi, Anil
Cannella, Dominique
Pennaneach, Vincent
Koundrioukoff, Stephane
Jacquinod, Michel
Forest, Eric
Podust, Vladimir
Fotedar, Arun
Fotedar, Rati
Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr(506) by cyclin-dependent kinases regulates binding to PCNA
description Replication factor C (RF-C) complex binds to DNA primers and loads PCNA onto DNA, thereby increasing the processivity of DNA polymerases. We have previously identified a distinct region, domain B, in the large subunit of human RF-C (RF-Cp145) which binds to PCNA. We show here that the functional interaction of RF-Cp145 with PCNA is regulated by cdk-cyclin kinases. Phosphorylation of either RF-Cp145 as a part of the RF-C complex or RF-Cp145 domain B by cdk-cyclin kinases inhibits their ability to bind PCNA. A cdk-cyclin phosphorylation site, Thr(506) in RF-Cp145, identified by mass spectrometry, is also phosphorylated in vivo. A Thr(506)→Ala RF-Cp145 domain B mutant is a poor in vitro substrate for cdk-cyclin kinase and, consequently, the ability of this mutant to bind PCNA was not suppressed by phosphorylation. By generating an antibody directed against phospho-Thr(506) in RF-Cp145, we demonstrate that phosphorylation of endogenous RF-Cp145 at Thr(506) is mediated by CDKs since it is abolished by treatment of cells with the cdk-cyclin inhibitor roscovitine. We have thus mapped an in vivo cdk-cyclin phosphorylation site within the PCNA binding domain of RF-Cp145.
author Salles-Passador, Isabelle
Munshi, Anil
Cannella, Dominique
Pennaneach, Vincent
Koundrioukoff, Stephane
Jacquinod, Michel
Forest, Eric
Podust, Vladimir
Fotedar, Arun
Fotedar, Rati
author_facet Salles-Passador, Isabelle
Munshi, Anil
Cannella, Dominique
Pennaneach, Vincent
Koundrioukoff, Stephane
Jacquinod, Michel
Forest, Eric
Podust, Vladimir
Fotedar, Arun
Fotedar, Rati
author_sort Salles-Passador, Isabelle
title Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr(506) by cyclin-dependent kinases regulates binding to PCNA
title_short Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr(506) by cyclin-dependent kinases regulates binding to PCNA
title_full Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr(506) by cyclin-dependent kinases regulates binding to PCNA
title_fullStr Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr(506) by cyclin-dependent kinases regulates binding to PCNA
title_full_unstemmed Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr(506) by cyclin-dependent kinases regulates binding to PCNA
title_sort phosphorylation of the pcna binding domain of the large subunit of replication factor c on thr(506) by cyclin-dependent kinases regulates binding to pcna
publisher Oxford University Press
publisher_facet Oxford University Press
publishDate 2003
url https://ncbi.nlm.nih.gov/pmc/articles/PMC212794/
https://ncbi.nlm.nih.gov/pubmed/12930972
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/nar/gkg692
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