[en] DNA double-strand breaks (DSBs) are genotoxic DNA lesions caused by ionizing radiation (IR) or mutagenic chemicals and potentially lead to chromosomal breakage, fragmentation, and translocation. Homologous recombination repair (HRR), classical non-homologous end-joining (C-NHEJ), and alternative non-homologous end-joining (Alt-NHEJ) are the major pathways employed by cells for repairing of DSBs. Therefore, their function is critical for protecting the genome stability in general but also for the development of radiation resistance e.g. in tumor cells. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mTOR signaling pathway functions at different levels and mechanisms of cell survival and apoptosis. Stimulated PI3K/AKT pathway activated by receptor tyrosine kinases or mutational hyperactivation has been reported in different human cancer entities. Akt/PKB is a serine/threonine kinase and exists in three isoforms known as Akt1 (PKBα), Akt2 (PKBβ) and Akt3 (PKBγ). In human malignancies, Akt activity plays a major role in tumor cell survival. Accumulating evidence exists with respect to the regulatory role of Akt isoforms in repair of DSBs through NHEJ pathway. Akt1 stimulates DNA-PKcs kinase activity, which is a necessary step for progression of DSB repair through NHEJ. Potential involvement of Akt in HRR has been also reported however, existing data are conflicting and need to be investigated in more details. The main aim of this thesis was to investigate the role of Akt isoforms in double strand breaks repair via homologous recombination repair. To achieve this, siRNA mediated knockdown as well as stable knock out approaches were applied to characterize the importance of Akt isoforms in the repair of DSBs executed by homologous recombination. Analyzing DSBs repair in human colorectal cancer cells after exposure to 4Gy irradiation indicated that HCT116 AKT1-KO and AKT2-KO cells present significantly enhanced levels of residual $\mathrm{\gamma <!--\; ??\; -->}$-H2AX foci in CENP-F positive cells (representing the S and G2 phase cells, i.e. cells which are competent for HRR). In comparison to wild type control cells inhibition of C-NHEJ and Alt-NHEJ using DNA-PK and PARP inhibitors resulted in elevated non repaired residual DNA-DSB in HCT116 AKT1- and especially AKT2-knockout cells. Moreover, Immunofluorescence analyses were performed to evaluate the regulation of Rad51 as a major protein of HRR by Akt. Analyses of Rad51 nuclear translocation and foci formation indicated that in the absence of Akt1 and Akt2 isoforms Rad51 nuclear accumulation is markedly reduced after radiation exposure. Furthermore, the results of colonogenic survival assays demonstrated that AKT1-KO and AKT2-KO cells in comparison to parental cells are significantly more sensitive to irradiation. It has been proven that deficiency of homologous recombination repair results in synthetic lethality after inhibition of poly-(adenosine diphosphate-ribose)-polymerase (PARP). In this project, PARP inhibitor Olaparib as a FDA approved drug for BRCA deficient tumors was used to evaluate the sensitivity of AKT depleted cells to inhibition of PARP. PARP inhibition in HCT116 cells by Olaparib showed that the clonogenic activity of cells is significantly reduced in AKT1-KO cells following irradiation. Interestingly, AKT2-KO were not able to form colonies after Olaparib treatment. These results indicate deficiency of HRR in AKT1-KO and AKT2-KO cells. The data obtained collectively suggest that both Akt isoforms Akt1 and Akt2 are important regulatory components in processes of DSB-repair via the homologous recombination mechanism.