title: SGO1 is involved in the DNA damage response in MYCN-amplified neuroblastoma cells.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.|Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Murakami-Tonami
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Yamagishi
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.|College of Pharmacy, Kinjo Gakuin University, 2-1723, Omori-cho, Moriyama-ku, Nagoya, 463-8521, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Inayoshi
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.|College of Pharmacy, Kinjo Gakuin University, 2-1723, Omori-cho, Moriyama-ku, Nagoya, 463-8521, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Inagaki
authors.affiliation: Department of Molecular Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kishida
authors.affiliation: Department of Molecular Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Komata
authors.affiliation: Department of Oncogenomics, Academic Medical Center, University of Amsterdam, Meibergdreef 9 1105 AZ Amsterdam, the Netherlands.
authors.lastname: Jan Koster
authors.affiliation: Department of Computer Science, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya, 466-8555, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takeuchi
authors.affiliation: Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: College of Pharmacy, Kinjo Gakuin University, 2-1723, Omori-cho, Moriyama-ku, Nagoya, 463-8521, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.|Department of Cancer Genetics, Program in Function Construction Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
authors.affiliation: Department of Biological Science, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Department of Molecular Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D004249:DNA Damage; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D007399:Interphase / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D000071447:N-Myc Proto-Oncogene Protein / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; C571825:MYCN protein, mouse; D000071447:N-Myc Proto-Oncogene Protein; C527733:shugoshin protein, mouse