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Inhibition of Karyopherin-α2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair

1
Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea
2
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(11), 2843; https://doi.org/10.3390/ijms20112843
Received: 3 May 2019 / Revised: 5 June 2019 / Accepted: 11 June 2019 / Published: 11 June 2019
(This article belongs to the Section Biochemistry)
Ionizing radiation (IR) has been widely used in the treatment of cancer. Radiation-induced DNA damage triggers the DNA damage response (DDR), which can confer radioresistance and early local recurrence by activating DNA repair pathways. Since karyopherin-α2 (KPNA2), playing an important role in nucleocytoplasmic transport, was significantly increased by IR in our previous study, we aimed to determine the function of KPNA2 with regard to DDR. Exposure to radiation upregulated KPNA2 expression in human colorectal cancer HT29 and HCT116 cells and breast carcinoma MDA-MB-231 cells together with the increased expression of DNA repair protein BRCA1. The knockdown of KPNA2 effectively increased apoptotic cell death via inhibition of BRCA1 nuclear import following IR. Therefore, we propose that KPNA2 is a potential target for overcoming radioresistance via interruption to DDR. View Full-Text
Keywords: ionizing radiation; karyopherin-α2; DNA repair; radioresistance; BRCA1 ionizing radiation; karyopherin-α2; DNA repair; radioresistance; BRCA1
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MDPI and ACS Style

Song, K.-H.; Jung, S.-Y.; Park, J.-I.; Ahn, J.; Park, J.K.; Um, H.-D.; Park, I.-C.; Hwang, S.-G.; Ha, H.; Song, J.-Y. Inhibition of Karyopherin-α2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair. Int. J. Mol. Sci. 2019, 20, 2843. https://doi.org/10.3390/ijms20112843

AMA Style

Song K-H, Jung S-Y, Park J-I, Ahn J, Park JK, Um H-D, Park I-C, Hwang S-G, Ha H, Song J-Y. Inhibition of Karyopherin-α2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair. International Journal of Molecular Sciences. 2019; 20(11):2843. https://doi.org/10.3390/ijms20112843

Chicago/Turabian Style

Song, Kyung-Hee, Seung-Youn Jung, Jeong-In Park, Jiyeon Ahn, Jong K. Park, Hong-Duck Um, In-Chul Park, Sang-Gu Hwang, Hunjoo Ha, and Jie-Young Song. 2019. "Inhibition of Karyopherin-α2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair" International Journal of Molecular Sciences 20, no. 11: 2843. https://doi.org/10.3390/ijms20112843

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