X DNA harm network in ArabidopsisClara Bourboussea,1, Neeraja Vegesnaa,b, and Julie A. Lawa,b,a Plant Molecular and Cellular Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037; and bDivision of Biological Sciences, University of California, San Diego, La Jolla, CAEdited by Julia Bailey-Serres, University of California, Riverside, CA, and approved November 14, 2018 (received for evaluation June 21, 2018)To combat DNA damage, organisms mount a DNA damage response (DDR) that outcomes in cell cycle regulation, DNA repair and, in extreme situations, cell death. Underscoring the importance of gene regulation in this response, studies in Arabidopsis have demonstrated that all the aforementioned processes depend on Benzyl-PEG8-t-butyl ester Data Sheet SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a NAC family transcription aspect (TF) that has been functionally equated to the mammalian tumor suppressor, p53. Even so, the expression networks connecting SOG1 to these processes stay largely unknown and, though the DDR spans from minutes to hours, most transcriptomic data correspond to single timepoint snapshots. Here, we generated transcriptional models of the DDR from GAMMA ()-irradiated wild-type and sog1 seedlings through a 24-hour time course using DREM, the Dynamic Regulatory Events Miner, Tetrahydrozoline custom synthesis revealing 11 coexpressed gene groups with distinct biological functions and cis-regulatory capabilities. Inside these networks, more chromatin immunoprecipitation and transcriptomic experiments revealed that SOG1 may be the important activator, straight targeting by far the most strongly up-regulated genes, including TFs, repair factors, and early cell cycle regulators, though three MYB3R TFs will be the key repressors, specifically targeting the most strongly down-regulated genes, which mostly correspond to G2/M cell cycle-regulated genes. Together these models reveal the temporal dynamics of the transcriptional events triggered by -irradiation and connects these events to TFs and biological processes more than a time scale commensurate with key processes coordinated in response to DNA damage, greatly expanding our understanding of the DDR.DNA harm responsepathways, too as the regulation of gene expression, cell cycle arrest, cell death, and endoreduplication (1, six, eight, 11). To gain insight in to the pathways and molecular interactions orchestrating these events, efforts in many organisms have focused on identifying and characterizing the crucial players, signaling cascades, and transcriptional applications that stem from the recognition of DNA damage. In plants, the SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1) transcription factor (TF) was identified from a DNA damage-suppressor screen (12) and was shown to become a major regulator from the DNA harm response (13). In the absence of SOG1, Arabidopsis plants exposed to DNA damaging agents show defects in gene regulation (13), cell cycle arrest (12), programmed cell death (14), endoreduplication (15), DNA repair, and genome stability (12, 13). These findings, as well as these displaying that SOG1 is regulated in an ATM-dependent manner by means of phosphorylation of conserved serine-glutamine motifs (16, 17), have led to SOG1 being functionally equated with p53 (eight, 18), a mammalian tumor suppressor that coordinates the DNA harm response and can also be phosphorylated in an ATM/ATR-dependent manner (19, 20). In spite of the central part of SOG1 within the DNA harm response, and the several research displaying SOG1 is vital for coping with DNA damage (125, 216), global expression de.
