RRC ID 45802
Author Murakami-Tonami Y, Ikeda H, Yamagishi R, Inayoshi M, Inagaki S, Kishida S, Komata Y, Jan Koster, Takeuchi I, Kondo Y, Maeda T, Sekido Y, Murakami H, Kadomatsu K.
Title SGO1 is involved in the DNA damage response in MYCN-amplified neuroblastoma cells.
Journal Sci Rep
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.
Volume 6
Pages 31615
Published 2016-8-19
DOI 10.1038/srep31615
PII srep31615
PMID 27539729
PMC PMC4990925
MeSH Animals Cell Cycle Proteins / biosynthesis* Cell Cycle Proteins / genetics Cell Line, Tumor DNA Damage* Gene Amplification* Gene Expression Regulation, Neoplastic* Interphase / genetics Mice Mice, Transgenic N-Myc Proto-Oncogene Protein / genetics N-Myc Proto-Oncogene Protein / metabolism* Neuroblastoma / genetics Neuroblastoma / metabolism* Neuroblastoma / pathology Transcription, Genetic*
IF 4.011
Times Cited 6
DNA material CSII-CMV-RfA-IRES2-Venus (RDB04388) CSII-CMV-Venus (RDB05553) CSII-CMV-mRFP (RDB06386).