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 Brondello, J.-M.
Right arrow Articles by Russell, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brondello, J.-M.
Right arrow Articles by Russell, P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 1999, p. 4262-4269, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Basis for the Checkpoint Signal Specificity That Regulates Chk1 and Cds1 Protein Kinases

Jean-Marc Brondello, Michael N. Boddy, Beth Furnari, and Paul Russell*

Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037

Received 19 January 1999/Returned for modification 9 February 1999/Accepted 24 March 1999

Six checkpoint Rad proteins (Rad1, Rad3, Rad9, Rad17, Rad26, and Hus1) are needed to regulate checkpoint protein kinases Chk1 and Cds1 in fission yeast. Chk1 is required to prevent mitosis when DNA is damaged by ionizing radiation (IR), whereas either kinase is sufficient to prevent mitosis when DNA replication is inhibited by hydroxyurea (HU). Checkpoint Rad proteins are required for IR-induced phosphorylation of Chk1 and HU-induced activation of Cds1. IR activates Cds1 only during the DNA synthesis (S) phase, whereas HU induces Chk1 phosphorylation only in cds1 mutants. Here, we investigate the basis of the checkpoint signal specificity of Chk1 phosphorylation and Cds1 activation. We show that IR fails to induce Chk1 phosphorylation in HU-arrested cells. Release from the HU arrest following IR causes substantial Chk1 phosphorylation. These and other data indicate that Cds1 prevents Chk1 phosphorylation in HU-arrested cells, which suggests that Cds1 actively suppresses a repair process that leads to Chk1 phosphorylation. Cds1 becomes more highly concentrated in the nucleus only during the S phase of the cell cycle. This finding correlates with S-phase specificity of IR-induced activation of Cds1. However, constitutive nuclear localization of Cds1 does not enhance IR-induced activation of Cds1. This result suggests that Cds1 activation requires DNA structures or protein activities that are present only during S phase. These findings help to explain how Chk1 and Cds1 respond to different checkpoint signals.

* Corresponding author. Mailing address: Department of Molecular Biology MB3, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-8273. Fax: (619) 784-2265. E-mail: prussell{at}scripps.edu.

Molecular and Cellular Biology, June 1999, p. 4262-4269, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Willis, N., Rhind, N. (2009). Mus81, Rhp51(Rad51), and Rqh1 Form an Epistatic Pathway Required for the S-Phase DNA Damage Checkpoint. Mol. Biol. Cell 20: 819-833 [Abstract] [Full Text]  
  • Dutta, C., Patel, P. K., Rosebrock, A., Oliva, A., Leatherwood, J., Rhind, N. (2008). The DNA Replication Checkpoint Directly Regulates MBF-Dependent G1/S Transcription. Mol. Cell. Biol. 28: 5977-5985 [Abstract] [Full Text]  
  • Segurado, M., Diffley, J. F.X. (2008). Separate roles for the DNA damage checkpoint protein kinases in stabilizing DNA replication forks. Genes Dev. 22: 1816-1827 [Abstract] [Full Text]  
  • Kunoh, T., Habu, T., Matsumoto, T. (2008). Involvement of fission yeast Clr6-HDAC in regulation of the checkpoint kinase Cds1. Nucleic Acids Res 36: 3311-3319 [Abstract] [Full Text]  
  • Diaz-Cuervo, H., Bueno, A. (2008). Cds1 Controls the Release of Cdc14-like Phosphatase Flp1 from the Nucleolus to Drive Full Activation of the Checkpoint Response to Replication Stress in Fission Yeast. Mol. Biol. Cell 19: 2488-2499 [Abstract] [Full Text]  
  • Bailis, J. M., Luche, D. D., Hunter, T., Forsburg, S. L. (2008). Minichromosome Maintenance Proteins Interact with Checkpoint and Recombination Proteins To Promote S-Phase Genome Stability. Mol. Cell. Biol. 28: 1724-1738 [Abstract] [Full Text]  
  • Chu, Z., Li, J., Eshaghi, M., Peng, X., Karuturi, R. K. M., Liu, J. (2007). Modulation of Cell Cycle-specific Gene Expressions at the Onset of S Phase Arrest Contributes to the Robust DNA Replication Checkpoint Response in Fission Yeas. Mol. Biol. Cell 18: 1756-1767 [Abstract] [Full Text]  
  • Shikata, M., Ishikawa, F., Kanoh, J. (2007). Tel2 Is Required for Activation of the Mrc1-mediated Replication Checkpoint. J. Biol. Chem. 282: 5346-5355 [Abstract] [Full Text]  
  • Callegari, A. J., Kelly, T. J. (2006). From the Cover: UV irradiation induces a postreplication DNA damage checkpoint. Proc. Natl. Acad. Sci. USA 103: 15877-15882 [Abstract] [Full Text]  
  • Miyabe, I., Morishita, T., Hishida, T., Yonei, S., Shinagawa, H. (2006). Rhp51-Dependent Recombination Intermediates That Do Not Generate Checkpoint Signal Are Accumulated in Schizosaccharomyces pombe rad60 and smc5/6 Mutants after Release from Replication Arrest. Mol. Cell. Biol. 26: 343-353 [Abstract] [Full Text]  
  • Purdy, A., Uyetake, L., Cordeiro, M. G., Su, T. T. (2005). Regulation of mitosis in response to damaged or incompletely replicated DNA require different levels of Grapes (Drosophila Chk1). J. Cell Sci. 118: 3305-3315 [Abstract] [Full Text]  
  • Sommariva, E., Pellny, T. K., Karahan, N., Kumar, S., Huberman, J. A., Dalgaard, J. Z. (2005). Schizosaccharomyces pombe Swi1, Swi3, and Hsk1 Are Components of a Novel S-Phase Response Pathway to Alkylation Damage. Mol. Cell. Biol. 25: 2770-2784 [Abstract] [Full Text]  
  • Meister, P., Taddei, A., Vernis, L., Poidevin, M., Gasser, S. M., Baldacci, G. (2005). Temporal separation of replication and recombination requires the intra-S checkpoint. JCB 168: 537-544 [Abstract] [Full Text]  
  • Maude, S. L., Enders, G. H. (2005). Cdk Inhibition in Human Cells Compromises Chk1 Function and Activates a DNA Damage Response. Cancer Res. 65: 780-786 [Abstract] [Full Text]  
  • Zachos, G., Rainey, M. D., Gillespie, D. A. F. (2005). Chk1-Dependent S-M Checkpoint Delay in Vertebrate Cells Is Linked to Maintenance of Viable Replication Structures. Mol. Cell. Biol. 25: 563-574 [Abstract] [Full Text]  
  • Noguchi, E., Noguchi, C., Du, L.-L., Russell, P. (2003). Swi1 Prevents Replication Fork Collapse and Controls Checkpoint Kinase Cds1. Mol. Cell. Biol. 23: 7861-7874 [Abstract] [Full Text]  
  • Du, L.-L., Nakamura, T. M., Moser, B. A., Russell, P. (2003). Retention but Not Recruitment of Crb2 at Double-Strand Breaks Requires Rad1 and Rad3 Complexes. Mol. Cell. Biol. 23: 6150-6158 [Abstract] [Full Text]  
  • Lambert, S., Mason, S. J., Barber, L. J., Hartley, J. A., Pearce, J. A., Carr, A. M., McHugh, P. J. (2003). Schizosaccharomyces pombe Checkpoint Response to DNA Interstrand Cross-Links. Mol. Cell. Biol. 23: 4728-4737 [Abstract] [Full Text]  
  • Weingartner, M., Pelayo, H. R., Binarova, P., Zwerger, K., Melikant, B., de la Torre, C., Heberle-Bors, E., Bogre, L. (2003). A plant cyclin B2 is degraded early in mitosis and its ectopic expression shortens G2-phase and alleviates the DNA-damage checkpoint. J. Cell Sci. 116: 487-498 [Abstract] [Full Text]  
  • Yu, Q., La Rose, J., Zhang, H., Takemura, H., Kohn, K. W., Pommier, Y. (2002). UCN-01 Inhibits p53 Up-Regulation and Abrogates {gamma}-Radiation-induced G2-M Checkpoint Independently of p53 by Targeting Both of the Checkpoint Kinases, Chk2 and Chk1. Cancer Res. 62: 5743-5748 [Abstract] [Full Text]  
  • Istfan, N. W., Chen, Z.-Y., Rex, S. (2002). Fish oil slows S phase progression and may cause upstream shift of DHFR replication origin ori-beta in CHO cells. Am. J. Physiol. Cell Physiol. 283: C1009-C1024 [Abstract] [Full Text]  
  • Fung, A. D., Ou, J., Bueler, S., Brown, G. W. (2002). A Conserved Domain of Schizosaccharomyces pombe dfp1+ Is Uniquely Required for Chromosome Stability following Alkylation Damage during S Phase. Mol. Cell. Biol. 22: 4477-4490 [Abstract] [Full Text]  
  • Marchetti, M. A., Kumar, S., Hartsuiker, E., Maftahi, M., Carr, A. M., Freyer, G. A., Burhans, W. C., Huberman, J. A. (2002). A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway. Proc. Natl. Acad. Sci. USA 99: 7472-7477 [Abstract] [Full Text]  
  • O'Neill, T., Giarratani, L., Chen, P., Iyer, L., Lee, C.-H., Bobiak, M., Kanai, F., Zhou, B.-B., Chung, J. H., Rathbun, G. A. (2002). Determination of Substrate Motifs for Human Chk1 and hCds1/Chk2 by the Oriented Peptide Library Approach. J. Biol. Chem. 277: 16102-16115 [Abstract] [Full Text]  
  • Vahteristo, P., Tamminen, A., Karvinen, P., Eerola, H., Eklund, C., Aaltonen, L. A., Blomqvist, C., Aittomaki, K., Nevanlinna, H. (2001). p53, CHK2, and CHK1 Genes in Finnish Families with Li-Fraumeni Syndrome: Further Evidence of CHK2 in Inherited Cancer Predisposition. Cancer Res. 61: 5718-5722 [Abstract] [Full Text]  
  • Kai, M., Tanaka, H., Wang, T. S.-F. (2001). Fission Yeast Rad17 Associates with Chromatin in Response to Aberrant Genomic Structures. Mol. Cell. Biol. 21: 3289-3301 [Abstract] [Full Text]  
  • Tanaka, K., Boddy, M. N., Chen, X.-B., McGowan, C. H., Russell, P. (2001). Threonine-11, Phosphorylated by Rad3 and ATM In Vitro, Is Required for Activation of Fission Yeast Checkpoint Kinase Cds1. Mol. Cell. Biol. 21: 3398-3404 [Abstract] [Full Text]  
  • Gottifredi, V., Karni-Schmidt, O., Shieh, S.-Y., Prives, C. (2001). p53 Down-Regulates CHK1 through p21 and the Retinoblastoma Protein. Mol. Cell. Biol. 21: 1066-1076 [Abstract] [Full Text]  
  • Takimoto, R., El-Deiry, W. S. (2001). DNA replication blockade impairs p53-transactivation. Proc. Natl. Acad. Sci. USA 98: 781-783 [Full Text]  
  • Gottifredi, V., Shieh, S.-Y., Taya, Y., Prives, C. (2001). p53 accumulates but is functionally impaired when DNA synthesis is blocked. Proc. Natl. Acad. Sci. USA 10.1073/pnas.021282898v1 [Abstract] [Full Text]  
  • Tan, S., Wang, T. S.-F. (2000). Analysis of Fission Yeast Primase Defines the Checkpoint Responses to Aberrant S Phase Initiation. Mol. Cell. Biol. 20: 7853-7866 [Abstract] [Full Text]  
  • Guo, Z., Kumagai, A., Wang, S. X., Dunphy, W. G. (2000). Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts. Genes Dev. 14: 2745-2756 [Abstract] [Full Text]  
  • Moser, B. A., Brondello, J.-M., Baber-Furnari, B., Russell, P. (2000). Mechanism of Caffeine-Induced Checkpoint Override in Fission Yeast. Mol. Cell. Biol. 20: 4288-4294 [Abstract] [Full Text]  
  • Takai, H., Tominaga, K., Motoyama, N., Minamishima, Y. A., Nagahama, H., Tsukiyama, T., Ikeda, K., Nakayama, K., Nakanishi, M., Nakayama, K.-i. (2000). Aberrant cell cycle checkpoint function and early embryonic death in Chk1-/- mice. Genes Dev. 14: 1439-1447 [Abstract] [Full Text]  
  • Guo, Z., Dunphy, W. G. (2000). Response of Xenopus Cds1 in Cell-free Extracts to DNA Templates with Double-stranded Ends. Mol. Biol. Cell 11: 1535-1546 [Abstract] [Full Text]  
  • Bessho, T., Sancar, A. (2000). Human DNA Damage Checkpoint Protein hRAD9 Is a 3' to 5' Exonuclease. J. Biol. Chem. 275: 7451-7454 [Abstract] [Full Text]  
  • Chehab, N. H., Malikzay, A., Appel, M., Halazonetis, T. D. (2000). Chk2/hCds1 functions as a DNA damage checkpoint in G1 by stabilizing p53. Genes Dev. 14: 278-288 [Abstract] [Full Text]  
  • Rhind, N, Russell, P (2000). Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways. J. Cell Sci. 113: 3889-3896 [Abstract]  
  • Griffiths, D, Uchiyama, M, Nurse, P, Wang, T. (2000). A novel mutant allele of the chromatin-bound fission yeast checkpoint protein Rad17 separates the DNA structure checkpoints. J. Cell Sci. 113: 1075-1088 [Abstract]  
  • SCHULTZ, L.B., CHEHAB, N.H., MALIKZAY, A., DITULLIO, R.A., STAVRIDI, E.S., HALAZONETIS, T.D. (2000). The DNA Damage Checkpoint and Human Cancer. Cold Spring Harb Symp Quant Biol 65: 489-498 [Abstract]  
  • Baber-Furnari, B. A., Rhind, N., Boddy, M. N., Shanahan, P., Lopez-Girona, A., Russell, P. (2000). Regulation of Mitotic Inhibitor Mik1 Helps to Enforce the DNA Damage Checkpoint. Mol. Biol. Cell 11: 1-11 [Abstract] [Full Text]  
  • Bell, D. W., Varley, J. M., Szydlo, T. E., Kang, D. H., Wahrer, D. C., Shannon, K. E., Lubratovich, M., Verselis, S. J., Isselbacher, K. J., Fraumeni, J. F., Birch, J. M., Li, F. P., Garber, J. E., Haber, D. A. (1999). Heterozygous Germ Line hCHK2 Mutations in Li-Fraumeni Syndrome. Science 286: 2528-2531 [Abstract] [Full Text]  
  • Hu, B., Zhou, X.-Y., Wang, X., Zeng, Z.-C., Iliakis, G., Wang, Y. (2001). The Radioresistance to Killing of A1-5 Cells Derives from Activation of the Chk1 Pathway. J. Biol. Chem. 276: 17693-17698 [Abstract] [Full Text]  
  • Gottifredi, V., Shieh, S.-Y., Taya, Y., Prives, C. (2001). From the Cover: p53 accumulates but is functionally impaired when DNA synthesis is blocked. Proc. Natl. Acad. Sci. USA 98: 1036-1041 [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»