For a paper appearing in Cell Systems, a University of California, San Diego- and J. David Gladstone Institute of Data Science and Biotechnology-led team presents a proteomics-based map of protein interactions involving 21 DNA damage response (DDR) proteins. Using affinity purification of the DDR proteins in the presence or absence of a DNA-damaging genotoxin, together with multi-omics profiling and multi-conditional network analyses, the investigators put together an interactive DNA damage response assemblies map (DDRAM) that spanned more than 100 assemblies and involved 605 proteins. From there, they relied on DDR functional assays, gene knockout or knockdown experiments, and other follow-up analyses to validate a subset of 28 proteins, highlighting a dozen new candidate DNA double-strand break repair-related proteins. "The map captures canonical repair mechanisms and proposes new DDR-associated proteins extending to stress, transport, and chromatin functions," the authors report. "We find that protein assemblies closely align with genetic dependencies in processing specific genotoxins and that proteins in multiple assemblies typically act in multiple genotoxin responses."