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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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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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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DOI: https://doi.org/10.1038/417197a
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