2010 Fiscal Year Final Research Report
Research for SUMO-3-involved DNA synthesis induction after X-ray irradiation in human cells
Project/Area Number |
20510049
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Risk sciences of radiation/Chemicals
|
Research Institution | Chiba University |
Principal Investigator |
SUGAYA Shigeru Chiba University, 大学院・医学研究院, 助教 (90334177)
|
Project Period (FY) |
2008 – 2010
|
Keywords | SUMO-2 / 3 / ヒト細胞 / X線 / DNA合成 / NM23-H1 |
Research Abstract |
Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome or basal cell nevus syndrome, is an autosomal dominant disorder that predisposes to both developmental defects and cancer. Fibroblast cells derived from (NBCCS) patients show increased levels of DNA synthesis after X-ray irradiation. We found that the induction of DNA synthesis after irradiation could be caused by the down-regulation of SUMO-3 gene expression in NBCCS cells. Eight hours after X-ray irradiation, an increase in DNA synthesis activity was found in HeLa cells with knockdown of SUMO-2/3. Under these conditions, the expression levels of Nm23-H1, a metastatic suppressor gene, was altered. The decrease of NM23-H1 protein after X-ray irradiation was confirmed by western blot analysis. As expected, treatment of HeLa cells with the siRNA of NM23-H1 resulted in the enhancement of DNA synthesis. These findings suggest that the intimate relationship with the expression of SUMO- SUMO-2/3 and the stability of NM23-H1 after X-ray irradiation, lead to the induction of DNA synthesis. Nm23-H1 may be modified by SUMO- SUMO-2/3 after X-ray irradiation. The reduction of Nm23-H1 seems to be casually related to the decrease in sumoylation, which in turn, is involved in the induction of DNA synthesis after X-ray irradiation.
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Sugaya S., Tanaka K., Akagi T., Kasetani T., Qiu-Ji Z., Guo W-Z., Udagawa A., Sugita K., Ohta R., Suzuki N.
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Journal Title
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Peer Reviewed
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