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A multi-scale map of protein assemblies in the DNA damage response.
Kratz, Anton; Kim, Minkyu; Kelly, Marcus R; Zheng, Fan; Koczor, Christopher A; Li, Jianfeng; Ono, Keiichiro; Qin, Yue; Churas, Christopher; Chen, Jing; Pillich, Rudolf T; Park, Jisoo; Modak, Maya; Collier, Rachel; Licon, Kate; Pratt, Dexter; Sobol, Robert W; Krogan, Nevan J; Ideker, Trey.
Affiliation
  • Kratz A; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA, USA.
  • Kim M; University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA 94158, USA; The J. David Gladstone Institute of Data Science and Biotechnology, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California San Francisco, San F
  • Kelly MR; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA.
  • Zheng F; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA, USA.
  • Koczor CA; University of South Alabama, Department of Pharmacology and Mitchell Cancer Institute, Mobile, AL 36604, USA.
  • Li J; University of South Alabama, Department of Pharmacology and Mitchell Cancer Institute, Mobile, AL 36604, USA.
  • Ono K; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA.
  • Qin Y; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA.
  • Churas C; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA.
  • Chen J; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA.
  • Pillich RT; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA.
  • Park J; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA, USA.
  • Modak M; University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA 94158, USA; The J. David Gladstone Institute of Data Science and Biotechnology, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California San Francisco, San F
  • Collier R; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA.
  • Licon K; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA.
  • Pratt D; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA.
  • Sobol RW; University of South Alabama, Department of Pharmacology and Mitchell Cancer Institute, Mobile, AL 36604, USA; Brown University, Department of Pathology and Laboratory Medicine and Legorreta Cancer Center, Providence, RI 02903, USA. Electronic address: rwsobol@brown.edu.
  • Krogan NJ; University of California San Francisco, Department of Cellular and Molecular Pharmacology, San Francisco, CA 94158, USA; The J. David Gladstone Institute of Data Science and Biotechnology, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California San Francisco, San F
  • Ideker T; University of California San Diego, Department of Medicine, San Diego, CA 92093, USA; The Cancer Cell Map Initiative, San Francisco and La Jolla, CA, USA. Electronic address: tideker@health.ucsd.edu.
Cell Syst ; 14(6): 447-463.e8, 2023 06 21.
Article in En | MEDLINE | ID: mdl-37220749
ABSTRACT
The DNA damage response (DDR) ensures error-free DNA replication and transcription and is disrupted in numerous diseases. An ongoing challenge is to determine the proteins orchestrating DDR and their organization into complexes, including constitutive interactions and those responding to genomic insult. Here, we use multi-conditional network analysis to systematically map DDR assemblies at multiple scales. Affinity purifications of 21 DDR proteins, with/without genotoxin exposure, are combined with multi-omics data to reveal a hierarchical organization of 605 proteins into 109 assemblies. The map captures canonical repair mechanisms and proposes new DDR-associated proteins extending to stress, transport, and chromatin functions. 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. Follow-up by DDR functional readouts newly implicates 12 assembly members in double-strand-break repair. The DNA damage response assemblies map is available for interactive visualization and query (ccmi.org/ddram/).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chromatin / DNA Repair Language: En Journal: Cell Syst Year: 2023 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chromatin / DNA Repair Language: En Journal: Cell Syst Year: 2023 Document type: Article Affiliation country: United States