Genomic Mapping Reveals Cisplatin Disruption of Protein Phosphorylation Signalling Genome-Wide

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ID: 316012
2026
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Abstract
Cisplatin is a DNA-targeting chemotherapeutic. Here we investigate how the cisplatin damaged gene loci are linked to specific protein-driven signalling pathways. An HMGB1a 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 cisplatin-damaged genes (CDGs) mapped with fold-enrichment > 1.5. Surprisingly, bioinformatics analysis demonstrates that cisplatin targets most of the human protein kinase 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 protein kinase 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 protein kinase genes.
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openalex_W7163635018 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Luyu Qi, Qun Luo, Yinzhu Hou, Y Xu, Wanchen Yu, Xingkai Liu, Bobo Xin, Yaolong Huang, Li X, Yanyan Zhang, S Wang, Peter J. Sadler, Y ZHAO, Fuyi Wang
Journal metallomics : integrated biometal science
Year 2026
DOI
10.1093/mtomcs/mfag016
URL
https://doi.org/10.1093/mtomcs/mfag016
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