Involvement of the PP2C-Like Phosphatase Ptc2p in the DNA Checkpoint Pathways of Saccharomyces cerevisiae

Corresponding author: Marie-Claude Marsolier, Service de Biochimie et de Génétique Moléculaire (Bat. 142), CEA/Saclay, F-91191 Gif-Sur-Yvette Cedex, France., marsolie{at}jonas.saclay.cea.fr (E-mail)

Communicating editor: M. JOHNSTON

RAD53 encodes a conserved protein kinase that acts as a central transducer in the DNA damage and the DNA replication checkpoint pathways in Saccharomyces cerevisiae. To identify new elements of these pathways acting with or downstream of RAD53, we searched for genes whose overexpression suppressed the toxicity of a dominant-lethal form of RAD53 and identified PTC2, which encodes a protein phosphatase of the PP2C family. PTC2 overexpression induces hypersensitivity to genotoxic agents in wild-type cells and is lethal to rad53, mec1, and dun1 mutants with low ribonucleotide reductase activity. Deleting PTC2 specifically suppresses the hydroxyurea hypersensitivity of mec1 mutants and the lethality of mec1. PTC2 is thus implicated in one or several functions related to RAD53, MEC1, and the DNA checkpoint pathways.

This article has been cited by other articles:

				J.-A. Kim and J. E. Haber Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating the DNA damage checkpoint when DNA repair is complete PNAS, January 27, 2009; 106(4): 1151 - 1156. [Abstract] [Full Text] [PDF]

				N. Lancelot, G. Charier, J. Couprie, I. Duband-Goulet, B. Alpha-Bazin, E. Quemeneur, E. Ma, M.-C. Marsolier-Kergoat, V. Ropars, J.-B. Charbonnier, et al. The checkpoint Saccharomyces cerevisiae Rad9 protein contains a tandem tudor domain that recognizes DNA Nucleic Acids Res., September 27, 2007; 35(17): 5898 - 5912. [Abstract] [Full Text] [PDF]

				G. Guillemain, E. Ma, S. Mauger, S. Miron, R. Thai, R. Guerois, F. Ochsenbein, and M.-C. Marsolier-Kergoat Mechanisms of Checkpoint Kinase Rad53 Inactivation after a Double-Strand Break in Saccharomyces cerevisiae Mol. Cell. Biol., May 1, 2007; 27(9): 3378 - 3389. [Abstract] [Full Text] [PDF]

				C. Clemenson and M.-C. Marsolier-Kergoat The Spindle Assembly Checkpoint Regulates the Phosphorylation State of a Subset of DNA Checkpoint Proteins in Saccharomyces cerevisiae Mol. Cell. Biol., December 15, 2006; 26(24): 9149 - 9161. [Abstract] [Full Text] [PDF]

				A. Gonzalez, A. Ruiz, R. Serrano, J. Arino, and A. Casamayor Transcriptional Profiling of the Protein Phosphatase 2C Family in Yeast Provides Insights into the Unique Functional Roles of Ptc1 J. Biol. Chem., November 17, 2006; 281(46): 35057 - 35069. [Abstract] [Full Text] [PDF]

				J. A. Sharp, G. Rizki, and P. D. Kaufman Regulation of Histone Deposition Proteins Asf1/Hir1 by Multiple DNA Damage Checkpoint Kinases in Saccharomyces cerevisiae Genetics, November 1, 2005; 171(3): 885 - 899. [Abstract] [Full Text] [PDF]

				C. Dubacq, A. Chevalier, and C. Mann The Protein Kinase Snf1 Is Required for Tolerance to the Ribonucleotide Reductase Inhibitor Hydroxyurea Mol. Cell. Biol., March 15, 2004; 24(6): 2560 - 2572. [Abstract] [Full Text] [PDF]

				R. Agarwal, Z. Tang, H. Yu, and O. Cohen-Fix Two Distinct Pathways for Inhibiting Pds1 Ubiquitination in Response to DNA Damage J. Biol. Chem., November 7, 2003; 278(45): 45027 - 45033. [Abstract] [Full Text] [PDF]

				A. L. Hughes and R. Friedman Parallel Evolution by Gene Duplication in the Genomes of Two Unicellular Fungi Genome Res., May 1, 2003; 13(5): 794 - 799. [Abstract] [Full Text] [PDF]

				B. L. Pike, A. Hammet, and J. Heierhorst Role of the N-terminal Forkhead-associated Domain in the Cell Cycle Checkpoint Function of the Rad53 Kinase J. Biol. Chem., April 20, 2001; 276(17): 14019 - 14026. [Abstract] [Full Text] [PDF]