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Cnd2 has dual roles in mitotic condensation and interphase

Nature volume 417, pages 197–202 (2002)Cite this article

Abstract

Chromosome condensation requires condensin1,2,3,4, which comprises five subunits5,6. Two of these subunits—both being structural maintenance of chromosome (SMC) proteins—are coiled-coils with globular terminal domains that interact with ATP and DNA. The remaining three, non-SMC subunits also have essential, albeit undefined, roles in condensation. Here we report that Cnd2 (ref. 6), a non-SMC subunit of fission yeast similar to Drosophila Barren7 and the budding yeast protein Brn1 (refs 8, 9), is required for both interphase and mitotic condensation. In cnd2-1 mutants, ultraviolet-induced DNA damage is not repaired, and cells arrested by hydroxyurea do not recover. A definitive defect of interphase is abolishment of Cds1 (a checkpoint kinase) activation in the presence of hydroxyurea in both cnd2-1 mutant cells and in cells where other condensin subunits have been genetically disrupted. In the absence of hydroxyurea, a G2 checkpoint delay occurred in cnd2-1 mutants in a manner dependent on Cds1 and ATM-like Rad3, but not Chk1 (refs 10–13), before the mitotic condensation defect. Furthermore, cnd2-1 was synthetic-lethal with mutations of excision repair, RecQ helicase and DNA replication enzymes. These interphase and mitotic defects provide insight into the mechanistic role of non-SMC subunits that interact with the globular SMC domains in the heteropentameric holocomplex14.

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Figure 1: Isolation of cnd2-1 and characterization of mutant protein.
Figure 2: Cnd2 is required for the recovery from HU-induced arrest and the activation of Cds1 in the presence of HU.
Figure 3: Cnd2 is required for repairing damaged DNA.
Figure 4: Interphase defect in cnd2-1 at 36 °C monitored by Rad3-, Crb2- and Cds1-dependent checkpoint control.
Figure 5: The role of Cnd2 in interphase.

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References

  1. Hirano, T. & Mitchison, T. J. A heterodimeric coiled-coil protein required for mitotic chromosome condensation. Cell 79, 449–458 (1994)

    Article  CAS  Google Scholar 

  2. Saka, Y. et al. Fission yeast cut3 and cut14, members of the ubiquitous protein family, are required for chromosome condensation and segregation in mitosis. EMBO J. 13, 4938–4952 (1994)

    Article  CAS  Google Scholar 

  3. Strunnikov, A. V., Hogan, E. & Koshland, D. SMC2, a Saccharomyces cerevisiae gene essential for chromosome segregation and condensation defines a subgroup within the SMC-family. Genes Dev. 9, 587–599 (1995)

    Article  CAS  Google Scholar 

  4. Kimura, K. & Hirano, T. ATP-dependent positive supercoiling of DNA by 13S condensin: a biochemical implication for chromosome condensation. Cell 90, 625–634 (1997)

    Article  CAS  Google Scholar 

  5. Hirano, T. SMC-mediated chromosome mechanics: a conserved scheme from bacteria to vertebrates? Genes Dev. 13, 11–19 (1999)

    Article  CAS  Google Scholar 

  6. Sutani, T. et al. Fission yeast condensin complex: essential roles of non-SMC subunits for condensation and Cdc2 phosphorylation of Cut3/SMC4. Genes Dev. 13, 2271–2283 (1999)

    Article  CAS  Google Scholar 

  7. Bhat, M. A., Philp, A. V., Glover, D. M. & Bellen, H. J. Chromatid segregation at anaphase requires the barren product, a novel chromosome-associated protein that interacts with Topoisomerase II. Cell 87, 1103–1114 (1996)

    Article  Google Scholar 

  8. Lavoie, B. D., Tuffo, K. M., Oh, S., Koshland, D. & Holm, C. Mitotic chromosome condensation requires Brn1p, the yeast homologue of Barren. Mol. Biol. Cell 11, 1293–1304 (2000)

    Article  CAS  Google Scholar 

  9. Ouspenski, II, Cabello, O. A. & Brinkley, B. R. Chromosome condensation factor Brn1p is required for chromatid separation in mitosis. Mol. Biol. Cell 11, 1305–1313 (2000)

    Article  CAS  Google Scholar 

  10. Bentley, N. J. et al. The Schizosaccharomyces pombe rad3 checkpoint gene. EMBO J. 15, 6641–6651 (1996)

    Article  CAS  Google Scholar 

  11. Saka, Y., Esashi, F., Matsusaka, T., Mochida, S. & Yanagida, M. Damage and replication checkpoint control in fission yeast is ensured by interactions of Crb2, a protein with BRCT-motif, with Cut5 and Chk1. Genes Dev. 11, 3387–3400 (1997)

    Article  CAS  Google Scholar 

  12. Murakami, H. & Okayama, H. A kinase from fission yeast responsible for blocking mitosis in S phase. Nature 374, 817–819 (1995)

    Article  ADS  CAS  Google Scholar 

  13. Boddy, M. N., Furnari, B., Mondesert, O. & Russell, P. Replication checkpoint enforced by kinases Cds1 and Chk1. Science 280, 909–912 (1998)

    Article  ADS  CAS  Google Scholar 

  14. Yoshimura, S. et al. Condensin architecture and interaction with DNA: regulatory non-SMC subunits bind to the head of SMC heterodimer. Curr. Biol. 12, 508–513 (2002)

    Article  CAS  Google Scholar 

  15. Yamashita, Y. M., Nakaseko, Y., Kumada, K., Nakagawa, T. & Yanagida, M. Fission yeast APC/cyclosome subunits, Cut20/Apc4 and Cut23/Apc8, in regulating metaphase–anaphase progression and cellular stress responses. Genes Cells 4, 445–463 (1999)

    Article  CAS  Google Scholar 

  16. Kearsey, S. E., Montgomery, S., Labib, K. & Lindner, K. Chromatin binding of the fission yeast replication factor mcm4 occurs during anaphase and requires ORC and cdc18. EMBO J. 19, 1681–1690 (2000)

    Article  CAS  Google Scholar 

  17. Tomonaga, T. et al. Characterization of fission yeast cohesin: essential anaphase proteolysis of Rad21 phosphorylated in the S phase. Genes Dev. 14, 2757–2770 (2000)

    Article  CAS  Google Scholar 

  18. Lindsay, H. D. et al. S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe. Genes Dev. 12, 382–395 (1998)

    Article  CAS  Google Scholar 

  19. Christensen, P. U., Bentley, N. J., Martinho, R. G., Nielsen, O. & Carr, A. M. Mik1 levels accumulate in S phase and may mediate an intrinsic link between S phase and mitosis. Proc. Natl Acad. Sci. USA 97, 2579–2584 (2000)

    Article  ADS  CAS  Google Scholar 

  20. Esashi, F. & Yanagida, M. Cdc2 phosphorylation of Crb2 is required for reestablishing cell cycle progression after the damage checkpoint. Mol. Cell 4, 167–174 (1999)

    Article  CAS  Google Scholar 

  21. Carr, A. M. et al. Evolutionary conservation of excision repair in Schizosaccharomyces pombe: evidence for a family of sequences related to the Saccharomyces cerevisiae RAD2 gene. Nucleic Acids Res. 21, 1345–1349 (1993)

    Article  CAS  Google Scholar 

  22. Yajima, H. et al. A eukaryotic gene encoding an endonuclease that specifically repairs DNA damaged by ultraviolet light. EMBO J. 14, 2393–2399 (1995)

    Article  CAS  Google Scholar 

  23. Muris, D. F. et al. Cloning the RAD51 homologue of Schizosaccharomyces pombe. Nucleic Acids Res. 21, 4586–4591 (1993)

    Article  CAS  Google Scholar 

  24. Stewart, E., Chapman, C. R., Al-Khodairy, F., Carr, A. M. & Enoch, T. rqh1+, a fission yeast gene related to the Bloom's and Werner's syndrome genes, is required for reversible S phase arrest. EMBO J. 16, 2682–2692 (1997)

    Article  CAS  Google Scholar 

  25. Murray, J. M., Lindsay, H. D., Munday, C. A. & Carr, A. M. Role of Schizosaccharomyces pombe RecQ homolog, recombination, and checkpoint genes in UV damage tolerance. Mol. Cell Biol. 17, 6868–6875 (1997)

    Article  CAS  Google Scholar 

  26. Sutani, T. & Yanagida, M. DNA renaturation activity of the SMC complex implicated in chromosome condensation. Nature 388, 798–801 (1997)

    Article  ADS  CAS  Google Scholar 

  27. Chuang, P. T., Albertson, D. G. & Meyer, B. J. DPY-27: a chromosome condensation protein homolog that regulates C. elegans dosage compensation through association with the X chromosome. Cell 79, 459–474 (1994)

    Article  CAS  Google Scholar 

  28. Lupo, R., Breiling, A., Bianchi, M. E. & Orlando, V. Drosophila chromosome condensation proteins Topoisomerase II and Barren colocalize with Polycomb and maintain Fab-7 PRE silencing. Mol. Cell 7, 127–136 (2001)

    Article  CAS  Google Scholar 

  29. Moreno, S., Hayles, J. & Nurse, P. Regulation of p34cdc2 protein kinase during mitosis. Cell 58, 361–372 (1989)

    Article  CAS  Google Scholar 

  30. Hutchins, J. R., Hughes, M. & Clarke, P. R. Substrate specificity determinants of the checkpoint protein kinase Chk1. FEBS Lett. 466, 91–95 (2000)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank R. Yu for reading the manuscript. This study was supported by the CREST Research Grant of Japan Science and Technology Corporation (JST) and the COE Grant of the Ministry of Education, Culture, Science and Technology. T.S. and T.T. were the recipients of JSPS (Japan Science Promotion Society) and JST postdoctoral fellowships, respectively.

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Author notes

  1. Takashi Sutani

    Present address: Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

  2. Takeshi Tomonaga

    Present address: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan

  3. Mitsuhiro Yanagida: Correspondence and requests for materials should be addressed to M.Y.

Authors and Affiliations

  1. Graduate School of Biostudies, Department of Gene Mechanisms, Kyoto University, Kitashirakawa-Oiwakecho, 606-8582, Sakyo-ku, Kyoto, Japan

    Nobuki Aono, Takashi Sutani, Takeshi Tomonaga, Satoru Mochida & Mitsuhiro Yanagida

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Correspondence to Mitsuhiro Yanagida.

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Aono, N., Sutani, T., Tomonaga, T. et al. Cnd2 has dual roles in mitotic condensation and interphase. Nature 417, 197–202 (2002). https://doi.org/10.1038/417197a

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