Letter | Published:

Separase-mediated cleavage of cohesin at interphase is required for DNA repair

Nature volume 430, pages 10441048 (26 August 2004) | Download Citation

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Abstract

Sister chromatids are held together by cohesins1. At anaphase, separase is activated by degradation of its inhibitory partner, securin2,3. Separase then cleaves cohesins4,5,6, thus allowing sister chromatid separation. Fission yeast securin (Cut2) has destruction boxes and a separase (Cut1) interaction site in the amino and carboxyl terminus, respectively7,8. Here we show that securin is essential for separase stability and also for proper repair of DNA damaged by ultraviolet, X-ray and γ-ray irradiation. The cut2EA2 mutant is defective in the repair of ultraviolet damage lesions, although the DNA damage checkpoint is activated normally. In double mutant analysis of ultraviolet sensitivity, checkpoint kinase chk1 (ref. 9) and excision repair rad13 (ref. 10) mutants were additive with cut2EA2, whereas recombination repair rhp51 (ref. 11) and cohesin subunit rad21 (ref. 12) mutants were not. Cohesin was hyper-modified on ultraviolet irradiation in a Rad3 kinase-dependent way13. Experiments using either mutant cohesin that cannot be cleaved by separase or a protease-dead separase provide evidence that this DNA repair function of securin–separase acts through the cleavage of cohesin. We propose that the securin–separase complex might aid DNA repair by removing local cohesin in interphase cells.

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Acknowledgements

We would like to thank C. Shimoda and T. Nakamura for the S. pombe genomic library, T. Carr, H. Okayama and N. Walworth for strains, and T. Matsumoto for introducing X-ray and γ-ray irradiation. This study was supported by the COE Grant of the Ministry of Education, Culture, Sports, Science and Technology of Japan. K.N. was a recipient of a predoctoral fellowship from the Japan Society for Promotion of Science.

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Affiliations

  1. Department of Biophysics, Graduate School of Science and

    • Koji Nagao
    •  & Mitsuhiro Yanagida
  2. Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501, Japan

    • Yoh Adachi
    •  & Mitsuhiro Yanagida
  3. Initial Research Project, Okinawa Institute of Science and Technology, Okinawa 904-2234, Japan

    • Koji Nagao
    •  & Mitsuhiro Yanagida

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Competing interests

The authors declare that they have no competing financial interests.

Corresponding author

Correspondence to Mitsuhiro Yanagida.

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https://doi.org/10.1038/nature02803

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