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Nucleoside analogues are molecules that share structural similarities with nucleosides and interfere with DNA replication. Many nucleoside analogues such as gemcitabine, a cytidine analogue, are an established part of cancer therapy. When integrated into the DNA, gemcitabine functions as a chain terminator and causes replication stalling, which leads to cell death. Other effects of Gemcitabine include dNTP pool depletion and inhibition of enzymes involved in DNA replication. Despite its established clinical use, the cellular mechanisms behind gemcitabine resistance and removal are not well understood. Previous research has shown that MRE11 is involved in the gemcitabine removal and thus contributes to resistance of cancer cells against gemcitabine. MRE11 is a core enzyme part of the MRN complex. It is frequently mutated in certain types of colorectal cancer. The MRN complex is involved in DNA double strand break detection and repair as well as other pathways such as topoisomerase removal. Mirin, a small molecule inhibitor, has been shown to be an inhibitor of the MRE11 exonuclease function. The research conducted in the context of this thesis shows that mirin exposure sensitises DT40 chicken B lymphocytes and human MRC5 lung fibroblasts to gemcitabine treatment. Furthermore, DT40 MRE11H129N/- cells innately deficient in MRE11 nuclease function showed sensitivity to gemcitabine as well, but no further sensitisation after mirin treatment. These results suggested that MRE11 exonuclease function might remove gemcitabine from the DNA. Analysis of the gemcitabine content of the DNA of gemcitabine-treated human and chicken cells via mass spectrometry showed that both mirin-treated and DT40 MRE11H129N/- cells have increased levels of genomic gemcitabine compared to control cells. Combined, these findings show that mirin specifically inhibits MRE11 exonuclease activity, and that MRE11 exonuclease activity contributes to the removal of gemcitabine from the DNA. Additional experiments with a library of S. pombe strains with mutations in genes involved in DNA damage detection and repair, cell cycle, and genome maintenance identified a number of mutants sensitive to treatment with hydroxyurea, gemcitabine, fludarabine, or cytarabine; homologous repair mutants and cell cycle checkpoint mutants displayed high sensitivity specifically. These findings show that DNA repair mechanism and knowledge of the genetic composition of cells such as mutations in cancer cells can be utilised to increase the efficiency of drug treatment, by personalising cancer treatment and tailoring treatment to individual patients.