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Site-specific phosphorylation of the DNA damage response mediator rad9 by cyclin-dependent kinases regulates activation of checkpoint kinase 1

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dc.contributor.author Abreu, Carla Manuela
dc.contributor.author Kumar, Ramesh
dc.contributor.author Hamilton, Danielle
dc.contributor.author Dawdy, Andrew William
dc.contributor.author Creavin, Kevin
dc.contributor.author Eivers, Sarah
dc.contributor.author Finn, Karen
dc.contributor.author Balsbaugh, Jeremy Lynn
dc.contributor.author O'Connor, Rosemary
dc.contributor.author Kiely, Patrick A.
dc.contributor.author Shabanowitz, Jeffrey
dc.contributor.author Hunt, Donal F
dc.contributor.author Grenon, Muriel
dc.contributor.author Lowndes, Noel Francis
dc.date.accessioned 2014-04-09T09:12:23Z
dc.date.available 2014-04-09T09:12:23Z
dc.date.issued 2013
dc.identifier.uri http://hdl.handle.net/10344/3770
dc.description peer-reviewed en_US
dc.description.abstract The mediators of the DNA damage response (DDR) are highly phosphorylated by kinases that control cell proliferation, but little is known about the role of this regulation. Here we show that cell cycle phosphorylation of the prototypical DDR mediator Saccharomyces cerevisiae Rad9 depends on cyclin-dependent kinase (CDK) complexes. We find that a specific G2/ M form of Cdc28 can phosphorylate in vitro the N-terminal region of Rad9 on nine consensus CDK phosphorylation sites. We show that the integrity of CDK consensus sites and the activity of Cdc28 are required for both the activation of the Chk1 checkpoint kinase and its interaction with Rad9. We have identified T125 and T143 as important residues in Rad9 for this Rad9/Chk1 interaction. Phosphorylation of T143 is the most important feature promoting Rad9/Chk1 interaction, while the much more abundant phosphorylation of the neighbouring T125 residue impedes the Rad9/Chk1 interaction. We suggest a novel model for Chk1 activation where Cdc28 regulates the constitutive interaction of Rad9 and Chk1. The Rad9/Chk1 complex is then recruited at sites of DNA damage where activation of Chk1 requires additional DDR–specific protein kinases. en_US
dc.language.iso eng en_US
dc.publisher Public Library of Science en_US
dc.relation.ispartofseries PLOS genetics;9 (4), e1003310
dc.relation.uri http://dx.doi.org/10.1371/journal.pgen.1003310
dc.subject DNA damage response en_US
dc.subject DDR en_US
dc.title Site-specific phosphorylation of the DNA damage response mediator rad9 by cyclin-dependent kinases regulates activation of checkpoint kinase 1 en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US


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