Journal
CELL CYCLE
Volume 13, Issue 7, Pages 1115-1131Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.27983
Keywords
condensin complex; DNA damage response; MYCN; neuroblastoma; synergistic lethal response
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Funding
- Global COE Program (Integrated functional molecular medicine for neuronal and neoplastic disorders)
- National Cancer Center Research and Development Fund [22-4]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [24590376, 23110002, 20390092]
- Grants-in-Aid for Scientific Research [24115702, 24590376, 24590377] Funding Source: KAKEN
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The condensin complex is required for chromosome condensation during mitosis; however, the role of this complex during interphase is unclear. Neuroblastoma is the most common extracranial solid tumor of childhood, and it is often lethal. In human neuroblastoma, MYCN gene amplification is correlated with poor prognosis. This study demonstrates that the gene encoding the condensin complex subunit SMC2 is transcriptionally regulated by MYCN. SMC2 also transcriptionally regulates DNA damage response genes in cooperation with MYCN. Downregulation of SMC2 induced DNA damage and showed a synergistic lethal response in MYCN-amplified/overexpression cells, leading to apoptosis in human neuroblastoma cells. Finally, this study found that patients bearing MYCN-amplified tumors showed improved survival when SMC2 expression was low. These results identify novel functions of SMC2 in DNA damage response, and we propose that SMC2 (or the condensin complex) is a novel molecular target for the treatment of MYCN-amplified neuroblastoma.
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