Genetic interaction (GI) not only suggests functional correlations between different genes in vivo, but also provides clues for understanding the potential biological function of a specific gene. Screening of GI is an important method for understanding GI between different genes. In this study, we selected sgf73⁺ as a query, which encodes a subunit of SAGA (Spt-Ada-Gcn5 acetyltransferase) complex deubiquitination module, to perform a large scale screening of GI in fission yeast. Our data showed that 164 genes had negative GIs whereas 42 genes had positive GIs with sgf73⁺. GO (Gene ontology) analysis indicated that these genes were enriched in several important biological processes, including chromatin modification, DNA damage repair, cellular response to stress, RNA transcription and so on. By using histone modification detection, we showed for the first time that loss of sgf73⁺ led to a decreased level of histone acetylation at H3K9 and H4K16 and an increased level of histone H3K4 methylation. Furthermore, the spot assay results showed that the sgf73∆ cells exhibited increased sensitivity to DNA damage agents, HU and CPT, and sgf73⁺ was involved in responses to hyperoxia stress. All these results suggested that sgf73⁺ plays important roles in chromatin modification, DNA damage repair and hyperoxia responses.