SGO1 is involved in the DNA damage response in MYCN-amplified neuroblastoma cells

نویسندگان

  • Yuko Murakami-Tonami
  • Haruna Ikeda
  • Ryota Yamagishi
  • Mao Inayoshi
  • Shiho Inagaki
  • Satoshi Kishida
  • Yosuke Komata
  • J K Jan Koster
  • Ichiro Takeuchi
  • Yutaka Kondo
  • Tohru Maeda
  • Yoshitaka Sekido
  • Hiroshi Murakami
  • Kenji Kadomatsu
چکیده

Shugoshin 1 (SGO1) is required for accurate chromosome segregation during mitosis and meiosis; however, its other functions, especially at interphase, are not clearly understood. Here, we found that downregulation of SGO1 caused a synergistic phenotype in cells overexpressing MYCN. Downregulation of SGO1 impaired proliferation and induced DNA damage followed by a senescence-like phenotype only in MYCN-overexpressing neuroblastoma cells. In these cells, SGO1 knockdown induced DNA damage, even during interphase, and this effect was independent of cohesin. Furthermore, MYCN-promoted SGO1 transcription and SGO1 expression tended to be higher in MYCN- or MYC-overexpressing cancers. Together, these findings indicate that SGO1 plays a role in the DNA damage response in interphase. Therefore, we propose that SGO1 represents a potential molecular target for treatment of MYCN-amplified neuroblastoma.

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2016