This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guillemain, G.
Right arrow Articles by Marsolier-Kergoat, M.-C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guillemain, G.
Right arrow Articles by Marsolier-Kergoat, M.-C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2007, p. 3378-3389, Vol. 27, No. 9
0270-7306/07/$08.00+0     doi:10.1128/MCB.00863-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Mechanisms of Checkpoint Kinase Rad53 Inactivation after a Double-Strand Break in Saccharomyces cerevisiae{triangledown}

Ghislaine Guillemain,1,{dagger},{ddagger} Emilie Ma,1,{dagger} Sarah Mauger,1 Simona Miron,2 Robert Thai,1 Raphaël Guérois,1 Françoise Ochsenbein,1 and Marie-Claude Marsolier-Kergoat1*

CEA, Direction des Sciences du Vivant, Institut de Biologie et de Technologies de Saclay, 91191 Gif-sur-Yvette Cedex, France,1 Institut Curie, INSERM U759, 91405 Orsay, France2

Received 15 May 2006/ Returned for modification 5 July 2006/ Accepted 9 February 2007

In Saccharomyces cerevisiae, double-strand breaks (DSBs) activate DNA checkpoint pathways that trigger several responses including a strong G2/M arrest. We have previously provided evidence that the phosphatases Ptc2 and Ptc3 of the protein phosphatase 2C type are required for DNA checkpoint inactivation after a DSB and probably dephosphorylate the checkpoint kinase Rad53. In this article we have investigated further the interactions between Ptc2 and Rad53. We showed that forkhead-associated domain 1 (FHA1) of Rad53 interacts with a specific threonine of Ptc2, T376, located outside its catalytic domain in a TXXD motif which constitutes an optimal FHA1 binding sequence in vitro. Mutating T376 abolishes Ptc2 interaction with the Rad53 FHA1 domain and results in adaptation and recovery defects following a DSB. We found that Ckb1 and Ckb2, the regulatory subunits of the protein kinase CK2, are necessary for the in vivo interaction between Ptc2 and the Rad53 FHA1 domain, that Ckb1 binds Ptc2 in vitro and that ckb1{Delta} and ckb2{Delta} mutants are defective in adaptation and recovery after a DSB. Our data thus strongly suggest that CK2 is the kinase responsible for the in vivo phosphorylation of Ptc2 T376.

* Corresponding author. Mailing address: Service de Biologie Intégrative et de Génétique Moléculaire, P.O. Box 22, CEA/Saclay, 91191 Gif-sur-Yvette Cedex, France. Phone: 33 1 69 08 83 54. Fax: 33 1 69 08 47 12. E-mail: mcmk{at}cea.fr

{triangledown} Published ahead of print on 26 February 2007.

{dagger} G.G. and E.M. contributed equally to this work.

{ddagger} Present address: Faculté de Médecine Necker, INSERM E363, 75730 Paris, France.

Molecular and Cellular Biology, May 2007, p. 3378-3389, Vol. 27, No. 9
0270-7306/07/$08.00+0     doi:10.1128/MCB.00863-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kim, J.-A., Haber, J. E. (2009). Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating the DNA damage checkpoint when DNA repair is complete. Proc. Natl. Acad. Sci. USA 106: 1151-1156 [Abstract] [Full Text]  
  • Mahajan, A., Yuan, C., Lee, H., Chen, E. S.-W., Wu, P.-Y., Tsai, M.-D. (2008). Structure and Function of the Phosphothreonine-Specific FHA Domain. Sci Signal 1: re12-re12 [Abstract] [Full Text]  
  • Luo, H., Li, Y., Mu, J.-J., Zhang, J., Tonaka, T., Hamamori, Y., Jung, S. Y., Wang, Y., Qin, J. (2008). Regulation of Intra-S Phase Checkpoint by Ionizing Radiation (IR)-dependent and IR-independent Phosphorylation of SMC3. J. Biol. Chem. 283: 19176-19183 [Abstract] [Full Text]  
  • Travesa, A., Duch, A., Quintana, D. G. (2008). Distinct Phosphatases Mediate the Deactivation of the DNA Damage Checkpoint Kinase Rad53. J. Biol. Chem. 283: 17123-17130 [Abstract] [Full Text]  
  • Nyswaner, K. M., Checkley, M. A., Yi, M., Stephens, R. M., Garfinkel, D. J. (2008). Chromatin-Associated Genes Protect the Yeast Genome From Ty1 Insertional Mutagenesis. Genetics 178: 197-214 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»