The ATR-Chk1 pathway plays a role in the generation of centrosome aberrations induced by Rad51C dysfunction

Mari Katsura, Takanori Tsuruga, Osamu Date, Takashi Yoshihara, Mari Ishida, Yoshitaka Tomoda, Miyuki Okajima, Motoki Takaku, Hitoshi Kurumizaka, Aiko Kinomura, Hiromu K. Mishima, Kiyoshi Miyagawa

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    14 Citations (Scopus)

    Abstract

    Rad51C is a central component of two complexes formed by five Rad51 paralogs in vertebrates. These complexes are involved in repairing DNA double-strand breaks through homologous recombination. Despite accumulating evidence suggesting that the paralogs may prevent aneuploidy by controlling centrosome integrity, Rad51C's role in maintaining chromosome stability remains unclear. Here we demonstrate that Rad51C deficiency leads to both centrosome aberrations in an ATR-Chk1-dependent manner and increased aneuploidy in human cells. While it was reported that Rad51C deficiency did not cause centrosome aberrations in interphase in hamster cells, such aberrations were observed in interphase in HCT116 cells with Rad51C dysfunction. Caffeine treatment and down-regulation of ATR, but not that of ATM, reduced the frequency of centrosome aberrations in the mutant cells. Silencing of Rad51C by RNA interference in HT1080 cells resulted in similar aberrations. Treatment with a Chk1 inhibitor and silencing of Chk1 also reduced the frequency in HCT116 mutants. Accumulation of Chk1 at the centrosome and nuclear foci of γH2AX were increased in the mutants. Moreover, the mutant cells had a higher frequency of aneuploidy. These findings indicate that the ATR-Chk1 pathway plays a role in increased centrosome aberrations induced by Rad51C dysfunction.

    Original languageEnglish
    Pages (from-to)3959-3968
    Number of pages10
    JournalNucleic Acids Research
    Volume37
    Issue number12
    DOIs
    Publication statusPublished - 2009

    ASJC Scopus subject areas

    • Genetics

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  • Cite this

    Katsura, M., Tsuruga, T., Date, O., Yoshihara, T., Ishida, M., Tomoda, Y., Okajima, M., Takaku, M., Kurumizaka, H., Kinomura, A., Mishima, H. K., & Miyagawa, K. (2009). The ATR-Chk1 pathway plays a role in the generation of centrosome aberrations induced by Rad51C dysfunction. Nucleic Acids Research, 37(12), 3959-3968. https://doi.org/10.1093/nar/gkp262