ArticleMetallomics : integrated biometal science2026
Genomic mapping reveals cisplatin disruption of protein phosphorylation signalling genome-wide.
Article in Metallomics : integrated biometal science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Cisplatin is a DNA-targeting chemotherapeutic. Here we investigate how the cisplatin-damaged gene (CDG) loci are linked to specific protein-driven signalling pathways. A human high mobility group protein 1 box a-based affinity probe has been constructed and 1,2-cisplatin-crosslinked DNA has been isolated before high throughput gene sequencing. Cisplatin damage to specific genes has been mapped in human lung cancer cells, and a total of 16 216 CDGs mapped with fold-enrichment >1.5. Surprisingly, bioinformatics analysis demonstrates that cisplatin targets most of the human protein kinase (PK) and phosphatase genes and is involved in 300 important cell signalling pathways (-log p > 4). The most associated key signalling pathways are sperm motility and protein kinase A. Notably, cisplatin damaged 85% (440) of human PK genes and 81% (110) of human protein phosphatase genes. This implies that cisplatin may disrupt protein phosphorylation signalling genome-wide, evidenced by a significant decrease in expression of a series of key PK genes.
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