In this thesis, the budding yeast Saccharomyces cerevisiae is used as a model system to investigate the role of the Holliday Junction resolvases Mus81 and Yen1 and their ability to maintain genome integrity by mediating DNA double-strand break repair. The role of the Swi-Snf related protein Uls1 in DNA repair and its interaction with Yen1 is examined by analysis of Yen1 overexpression in various mutant strains subjected to DNA damage. Additionally, the effect of protein modification by the small Ubiquitin-like modifier SUMO on strains lacking these proteins is elucidated in conditions challenging the cells with DNA damage. Furthermore, the roles of Mus81, Yen1 and Uls1 during meiotic recombination are investigated. Finally, the effect of SUMO targeted Ubiquitin ligases on modification of the sliding clamp PCNA is tested.