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Genomic mapping reveals cisplatin disruption of protein phosphorylation signalling genome-wide

Luyu Qi1,2, Qun Luo1,2, Yinzhu Hou1,2

  • 1Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Metallomics : Integrated Biometal Science
|June 5, 2026
PubMed

Insights

Cisplatin chemotherapy damages DNA, surprisingly impacting most human protein kinase and phosphatase genes. This suggests cisplatin disrupts genome-wide protein phosphorylation signaling pathways, affecting cell functions like sperm motility.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • Cisplatin is a widely used DNA-targeting chemotherapeutic agent in cancer treatment.
  • Understanding how cisplatin-induced DNA damage affects cellular signaling is crucial for optimizing its efficacy and managing side effects.

Purpose of the Study:

  • To investigate the link between cisplatin-damaged gene loci and specific protein-driven signaling pathways.
  • To map cisplatin-induced DNA damage across the human genome and identify targeted genes and pathways.

Main Methods:

  • Construction of an HMGB1a-based affinity probe to isolate cisplatin-crosslinked DNA.
  • High-throughput gene sequencing to map cisplatin damage to specific genes in human lung cancer cells.
  • Bioinformatic analysis to identify enriched signaling pathways associated with damaged genes.

Main Results:

  • Identified 16,216 cisplatin-damaged genes (CDGs) with fold-enrichment > 1.5.
  • Demonstrated that cisplatin targets a significant proportion of human protein kinase (85%) and phosphatase (81%) genes.
  • Revealed involvement of cisplatin-damaged genes in approximately 300 important cell signaling pathways, notably sperm motility and protein kinase A.

Conclusions:

  • Cisplatin extensively disrupts protein phosphorylation signaling pathways genome-wide.
  • The observed decrease in key protein kinase gene expression suggests a mechanism for cisplatin's therapeutic and potentially toxic effects.
  • Findings highlight the broad impact of cisplatin on cellular signaling networks beyond direct DNA damage.

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