MRE11 is involved in many pathways of DNA damage recognition and repair, and in the overall maintenance of genomic stability. Synthetic lethality is an anticancer therapy approach that exploits the inherent differences between cancerous and non-cancerous cells, and one such strategy involves the targeting to DNA repair proteins. Cancers are commonly deficient in DNA damage recognition and repair pathways, due to increased mutation rates providing more opportunity for chance selective advantage to occur. This, however, results in an increased reliance on alternative repair pathways which can then be targeted by specific small molecule inhibitors to result in synthetic lethality. MRE11 is one such repair factor that has been identified as a potential anticancer target, with its inhibition previously having been shown to sensitise cells to the cancer drugs camptothecin and gemcitabine. Moreover, novel MRE11 inhibitors with improved pharmacological properties compared to those currently available are currently in development. This project screens a variety of selected inhibitors of DNA repair proteins for synthetic interaction with MRE11 inhibition, with the aim of identifying synthetic lethal interactions that could be exploited by novel MRE11 inhibitors clinically. It is shown that synthetic lethal interactions were present for PARP, FEN1 and ATR with MRE11 exonuclease in DT40 MRE11+/- cells, with this synthetic lethality also observed for PARP and FEN1 in TK6WT/-. However, MRE11 exonuclease inhibition seems to rescue the effects of DNA2 inhibition in DT40 MRE11+/-, and RAD51 inhibition in TK6WT/-, while no effects were shown with the addition of MRE11 exonuclease inhibition for DNA-PK, WRN and ATM in DT40 MRE11+/-. As MRE11 has been shown to have the ability to remove protein-DNA blocks, such as topoisomerase complexes, from the DNA, it was thought that PARP-trapping inhibitors might work synergistically with MRE11 inhibition, and so inhibitors with different PARP-trapping capabilities were tested. Some evidence of further synthetic genetic interaction between potent PARP-trapper Talazoparib and mirin was observed in TK6WT/-, but overall this line of study was inconclusive and requires further investigation. This project provides evidence for synthetic genetic interactions between a variety of DNA repair factors and MRE11 inhibition, that can be used in further investigation with novel MRE11 inhibitors for use in personalised treatment of cancers expressing defects in these DNA repair pathways.