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 Collura, A.
Right arrow Articles by Francesconi, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Collura, A.
Right arrow Articles by Francesconi, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2005, p. 7889-7899, Vol. 25, No. 17
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.17.7889-7899.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Fission Yeast Crb2/Chk1 Pathway Coordinates the DNA Damage and Spindle Checkpoint in Response to Replication Stress Induced by Topoisomerase I Inhibitor

Ada Collura, Joel Blaisonneau, Giuseppe Baldacci, and Stefania Francesconi*

CNRS UMR 2027—Institut Curie, Batiment 110, Centre Universitaire d'Orsay, 91405 Orsay, France

Received 22 December 2004/ Returned for modification 25 January 2005/ Accepted 3 June 2005

Living organisms experience constant threats that challenge their genome stability. The DNA damage checkpoint pathway coordinates cell cycle progression with DNA repair when DNA is damaged, thus ensuring faithful transmission of the genome. The spindle assembly checkpoint inhibits chromosome segregation until all chromosomes are properly attached to the spindle, ensuring accurate partition of the genetic material. Both the DNA damage and spindle checkpoint pathways participate in genome integrity. However, no clear connection between these two pathways has been described. Here, we analyze mutants in the BRCT domains of fission yeast Crb2, which mediates Chk1 activation, and provide evidence for a novel function of the Chk1 pathway. When the Crb2 mutants experience damaged replication forks upon inhibition of the religation activity of topoisomerase I, the Chk1 DNA damage pathway induces sustained activation of the spindle checkpoint, which in turn delays metaphase-to-anaphase transition in a Mad2-dependent fashion. This new pathway enhances cell survival and genome stability when cells undergo replicative stress in the absence of a proficient G2/M DNA damage checkpoint.

* Corresponding author. Mailing address: CNRS UMR 2027—Institut Curie, Batiment 110, Centre Universitaire d'Orsay, 91405 Orsay, France. Phone: (33) 01 69 86 31 39. Fax: (33) 01 69 86 94 29. E-mail: sfrances{at}curie.u-psud.fr.

Molecular and Cellular Biology, September 2005, p. 7889-7899, Vol. 25, No. 17
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.17.7889-7899.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Froget, B., Blaisonneau, J., Lambert, S., Baldacci, G. (2008). Cleavage of Stalled Forks by Fission Yeast Mus81/Eme1 in Absence of DNA Replication Checkpoint. Mol. Biol. Cell 19: 445-456 [Abstract] [Full Text]  
  • Ahmed, S., Dul, B., Qiu, X., Walworth, N. C. (2007). Msc1 Acts Through Histone H2A.Z to Promote Chromosome Stability in Schizosaccharomyces pombe. Genetics 177: 1487-1497 [Abstract] [Full Text]  
  • Clemenson, C., Marsolier-Kergoat, M.-C. (2006). The Spindle Assembly Checkpoint Regulates the Phosphorylation State of a Subset of DNA Checkpoint Proteins in Saccharomyces cerevisiae. Mol. Cell. Biol. 26: 9149-9161 [Abstract] [Full Text]  
  • Blake, D., Luke, B., Kanellis, P., Jorgensen, P., Goh, T., Penfold, S., Breitkreutz, B.-J., Durocher, D., Peter, M., Tyers, M. (2006). The F-Box Protein Dia2 Overcomes Replication Impedance to Promote Genome Stability in Saccharomyces cerevisiae. Genetics 174: 1709-1727 [Abstract] [Full Text]  
  • Taricani, L., Wang, T. S.F. (2006). Rad4TopBP1, a Scaffold Protein, Plays Separate Roles in DNA Damage and Replication Checkpoints and DNA Replication. Mol. Biol. Cell 17: 3456-3468 [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»