Journal Article

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

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

2016

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/109 / 13/31 / 13/89 / 14/19 / 38/15 / 38/39 / 38/61 / 631/67/395 / 631/67/68 / Animals / Cell Cycle Proteins - biosynthesis / Cell Cycle Proteins - genetics / Cell Line, Tumor / DNA Damage / Gene Amplification / Gene Expression Regulation, Neoplastic / Humanities and Social Sciences / Interphase - genetics / Mice / Mice, Transgenic / multidisciplinary / N-Myc Proto-Oncogene Protein - genetics / N-Myc Proto-Oncogene Protein - metabolism / Neuroblastoma - genetics / Neuroblastoma - metabolism / Neuroblastoma - pathology / Science / Transcription, Genetic