The selective continued linkage of centromeres from mitosis to interphase in the absence of mammalian separase

Kazuki Kumada, Ryoji Yao, Tokuichi Kawaguchi, Mika Karasawa, Yutaka Hoshikawa, Koji Ichikawa, Yoshinobu Sugitani, Issei Imoto, Johji Inazawa, Minoru Sugawara, Mitsuhiro Yanagida, Tetsuo Noda

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62 Citations (Scopus)

Abstract

Separase is an evolutionarily conserved protease that is essential for chromosome segregation and cleaves cohesin Scc1/Rad21, which joins the sister chromatids together. Although mammalian separase also functions in chromosome segregation, our understanding of this process in mammals is still incomplete. We generated separase knockout mice, reporting an essential function for mammalian separase. Separase-deficient mouse embryonic fibroblasts exhibited severely restrained increases in cell number, polyploid chromosomes, and amplified centrosomes. Chromosome spreads demonstrated that multiple chromosomes connected to a centromeric region. Live observation demonstrated that the chromosomes of separase-deficient cells condensed, but failed to segregate, although subsequent cytokinesis and chromosome decondensation proceeded normally. These results establish that mammalian separase is essential for the separation of centromeres, but not of the arm regions of chromosomes. Other cell cycle events, such as mitotic exit, DNA replication, and centrosome duplication appear to occur normally. We also demonstrated that heterozygous separase-deficient cells exhibited severely restrained increases in cell number with apparently normal mitosis in the absence of securin, which is an inhibitory partner of separase.

Original languageEnglish
Pages (from-to)835-846
Number of pages12
JournalJournal of Cell Biology
Volume172
Issue number6
DOIs
Publication statusPublished - 2006 Mar 13

ASJC Scopus subject areas

  • Cell Biology

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    Kumada, K., Yao, R., Kawaguchi, T., Karasawa, M., Hoshikawa, Y., Ichikawa, K., Sugitani, Y., Imoto, I., Inazawa, J., Sugawara, M., Yanagida, M., & Noda, T. (2006). The selective continued linkage of centromeres from mitosis to interphase in the absence of mammalian separase. Journal of Cell Biology, 172(6), 835-846. https://doi.org/10.1083/jcb.200511126