Molecular Linkage Between DNA Damage Response And Autophagy In Saccharomy Cescerevisiae

Based on whole genome sequencing of Saccharomy cescerevisiae, about6000genes and Open Reading Frames (ORFs) with unknown functions have been identified. In the present study, we systematically analyzed the potential functions and molecular mechanisms of a new gene IRC4.Based on genetic manipulation assays, we showed that RAD24, one of the important DNA damage checkpoint sensors, genetically interacted with IRC4, because irc4△rad24△cells showed both growth defect and cell cycle progression defect. We further demonstrated that irc4△resulted in up-regulation of the spontaneous Rad52foci levels, suggesting that Irc4involves in the regulation pathway of DNA damage responses. In addition, we presented evidence that the C-terminus (amino acid139-189) of Irc4was responsible for the formation of the spontaneous Rad52foci.Our results suggested that Irc4and Atgl worked in the same pathway to regulate the levels of spontaneous Rad52foci. We also showed that Irc4and Atgl had a strong protein-protein interaction both in vivo and in vitro. Importantly, Irc4showed its negative regulating role in the formation of phagophore assembly site (PAS), and it contributed to autophagy as well.Taken together, we suggest that Irc4is a molecular linkage between DNA damage response and antophagy.Elgl plays important roles in cell cycle regulation and DNA damage response. Our results showed that Irc4and Elgl functioned on the the levels of spontaneous Rad52foci in two separate pathways. Moreover, microarray analysis showed the diffenerntial profiling of gene expressions in the cell-cycle process of elgl△cells compared to wild type. In addition, we showed that elgl△cells was more sensitive to DNA damage agent MMS than wild type (WT), and the levels of some genes in DNA damage response were changed as well. On the other hand, elgl mutation caused cell cycle progression defect, which may be related to its role in the maturation of Okazaki fragments. Therefore, we suggest that Elgl links DNA damage response to cell cycle regulation system.