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Open AccessArticle

Depletion of Akt1 and Akt2 Impairs the Repair of Radiation-Induced DNA Double Strand Breaks via Homologous Recombination

1
Division of Radiobiology and Molecular Environmental Research, Department of Radiation Oncology, University of Tübingen, Röntgenweg 11, 72076 Tübingen, Germany
2
DKFZ Partner Site Tübingen, German Cancer Consortium, German Cancer Research Center, 69120 Heidelberg, Germany
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(24), 6316; https://doi.org/10.3390/ijms20246316
Received: 10 October 2019 / Revised: 4 December 2019 / Accepted: 11 December 2019 / Published: 14 December 2019
(This article belongs to the Section Molecular Oncology)
Homologous recombination repair (HRR), non-homologous end-joining (NHEJ) and alternative NHEJ are major pathways that are utilized by cells for processing DNA double strand breaks (DNA-DSBs); their function plays an important role in the radiation resistance of tumor cells. Conflicting data exist regarding the role of Akt in homologous recombination (HR), i.e., the regulation of Rad51 as a major protein of this pathway. This study was designed to investigate the specific involvement of Akt isoforms in HRR. HCT116 colon cancer cells with stable AKT-knock-out and siRNA-mediated AKT-knockdown phenotypes were used to investigate the role of Akt1 and Akt2 isoforms in HR. The results clearly demonstrated that HCT116 AKT1-KO and AKT2-KO cells have a significantly reduced Rad51 foci formation 6 h post irradiation versus parental cells. Depletion of Akt1 and Akt2 protein levels as well as inhibition of Akt kinase activity resulted in an increased number of residual-γH2AX in CENP-F positive cells mainly representing the S and G2 phase cells. Furthermore, inhibition of NHEJ and HR using DNA-PK and Rad51 antagonists resulted in stronger radiosensitivity of AKT1 and AKT2 knockout cells versus wild type cells. These data collectively show that both Akt1 and Akt2 are involved in DSBs repair through HRR. View Full-Text
Keywords: DSBs; HRR; Akt isoforms; human colorectal cancer DSBs; HRR; Akt isoforms; human colorectal cancer
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MDPI and ACS Style

Mohammadian Gol, T.; Rodemann, H.P.; Dittmann, K. Depletion of Akt1 and Akt2 Impairs the Repair of Radiation-Induced DNA Double Strand Breaks via Homologous Recombination. Int. J. Mol. Sci. 2019, 20, 6316. https://doi.org/10.3390/ijms20246316

AMA Style

Mohammadian Gol T, Rodemann HP, Dittmann K. Depletion of Akt1 and Akt2 Impairs the Repair of Radiation-Induced DNA Double Strand Breaks via Homologous Recombination. International Journal of Molecular Sciences. 2019; 20(24):6316. https://doi.org/10.3390/ijms20246316

Chicago/Turabian Style

Mohammadian Gol, Tahereh; Rodemann, H. P.; Dittmann, Klaus. 2019. "Depletion of Akt1 and Akt2 Impairs the Repair of Radiation-Induced DNA Double Strand Breaks via Homologous Recombination" Int. J. Mol. Sci. 20, no. 24: 6316. https://doi.org/10.3390/ijms20246316

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