A multi-scale map of protein assemblies in the DNA damage response

• DOI: 10.1016/j.cels.2023.04.007
• Publication Date: 2023-05-22T14:30:33Z
• Authors: Anton Kratz; Minkyu Kim; Marcus R. Kelly; Fan Zheng; Christopher A. Ko...; Jianfeng Li; Keiichiro Ono; Yue Qin; Christopher Churas; Jing Chen; Rudolf T. Pillich; Jisoo Park; Maya Modak; Rachel Collier; Kate Licon; Dexter Pratt; Robert W. Sobol; Nevan J. Krogan; Trey Ideker
• Keywords: 570; DNA Repair; protein networks; protein assemblies; double-strand break repair; single-strand break repair; systems biology; multi-omics; DNA damage response; visualization; Chromatin; DNA Damage

The DNA damage response (DDR) ensures error-free replication and transcription is disrupted in numerous diseases. An ongoing challenge to determine the proteins orchestrating DDR their organization into complexes, including constitutive interactions those responding genomic insult. Here, we use multi-conditional network analysis systematically map assemblies at multiple scales. Affinity purifications of 21 proteins, with/without genotoxin exposure, are combined with multi-omics data reveal a hierarchical 605 109 assemblies. captures canonical repair mechanisms proposes new DDR-associated extending stress, transport, chromatin functions. We find that protein closely align genetic dependencies processing specific genotoxins typically act responses. Follow-up by functional readouts newly implicates 12 assembly members double-strand-break repair. available for interactive visualization query (ccmi.org/ddram/).