Conditional Genetic Interactions of RTT107 SLX4 and HRQ1 Reveal Dynamic Networks upon DNA Damage in S. cerevisiae

摘要

The DNA damage response (DDR) is a dynamic process that is crucial for protecting the cell from challenges to genome integrity. Although many genome-wide studies in Saccharomyces cerevisiae have identified genes that contribute to resistance to DNA-damaging agents, more work is needed to elucidate the changes in genetic interaction networks in response to DNA lesions. Here we used conditional epistatic miniarray profiling to analyze the genetic interaction networks of the DDR genes , , and under three DNA-damaging conditions: camptothecin, hydroxyurea, and methyl methanesulfonate. and its interaction partner are targets of the checkpoint kinase , which is central to the DDR-signaling cascades. recently was identified as a novel member of the RecQ helicase family in S. cerevisiae but is still poorly characterized. The conditional genetic networks that we generated revealed functional insights into all three genes and showed that there were varied responses to different DNA damaging agents. We observed that had more genetic interactions under camptothecin conditions than or , suggesting that has an important role in response to this type of DNA lesion. Although and function together, they also had many distinct genetic interactions. In particular, and showed contrasting genetic interactions for a few genes, which we validated with independently constructed strains. Interestingly, had a genetic interaction profile that correlated with that of href="http://www.yeastgenome.org/cgi-bin/locus.fpl?dbid=S000004125" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=4065249&issue-id=239266&journal-id=1684&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">SLX4 and both were enriched for very similar gene ontology terms, suggesting that they function together in the DDR.