2023-05-22 カリフォルニア大学サンディエゴ校(UCSD)
◆DNAの損傷は疾患の原因であり、がんなどの病気の特徴です。この研究により、DNA損傷応答(DDR)の複雑さと機能を明らかにすることで、治療の新たな可能性が提案されます。
◆研究者はDDRのタンパク質アセンブリのマルチスケール地図を作成し、新しい修復メカニズムとストレス、トランスポート、クロマチン機能に関連する新しいDDR関連タンパク質を提案しました。また、他の科学者が特定の興味を持つタンパク質とDDRの相互作用を調査するためのインタラクティブなソフトウェアも開発されました。
<関連情報>
- https://today.ucsd.edu/story/a-new-map-reveals-the-complicated-world-in-which-cells-seek-to-repair-damaged-dna
- https://www.cell.com/cell-systems/fulltext/S2405-4712(23)00116-3
DNA損傷応答におけるタンパク質集合体のマルチスケールマップ A multi-scale map of protein assemblies in the DNA damage response
Anton Kratz,Minkyu Kim,Marcus R. Kelly,Fan Zheng,Christopher A. Koczor,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
Cell Systems Published:May 22, 2023
DOI:https://doi.org/10.1016/j.cels.2023.04.007
Highlights
•The DNA damage response assemblies map (DDRAM) is a proteomics-driven map of DDR assemblies
•Complete interaction profiles for 21 factors, ± DNA damage, integrated with public data
•A total of 605 proteins organized in a hierarchy of 109 assemblies
•Functional readouts newly implicate 12 proteins in double-strand-break repair
Summary
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/).
