Target intelligence / Profile preview

DNA (Crosslinking) (DNA Crosslinking)

Target
DNA Crosslinking
Molecular classification
DNA, Other
01

Overview

DNA crosslinking refers to the formation of covalent bonds between two nucleotides within DNA, either on the same strand (intrastrand) or between opposite strands (interstrand). This process can be triggered by various exogenous agents (such as chemotherapeutic drugs, radiation, or environmental toxins) or endogenous factors. Crosslinks disrupt essential cellular processes such as replication and transcription, leading to cell death. It is a key target in cancer therapy using crosslinking agents that induce apoptosis in rapidly dividing cells. Cells have evolved complex repair pathways for resolving these lesions involving NER, homologous recombination, and base excision repair pathways.

Other names
DNA AdductsDNA Interstrand CrosslinksDNA Intrastrand CrosslinksDNA-Protein Crosslinks
02

Mechanism of action

Drugs like cisplatin and nitrogen mustards introduce covalent crosslinks between DNA strands, particularly at guanine residues, which disrupts DNA replication and transcription, leading to cell cycle arrest and apoptosis, especially in rapidly dividing cells such as cancer cells.

03

Biological functions

DNA Replication InhibitionTranscription InhibitionCell DeathGenome IntegrityDNA Repair
04

Disease associations

CancerGenetic DisordersAging
05

Safety considerations

Off-target effects leading to toxicity in healthy cellsDevelopment of drug resistance due to increased DNA repair capacity in cancer cellsSecondary malignancies due to DNA damage in non-cancerous cellsMyelosuppressionNephrotoxicity
06

Interacting drugs

Cisplatin

2 more in the full profile.

07

Biomarkers

Levels of DNA adductsExpression of DNA repair proteins (e.g., XPF-ERCC1, BRCA1)Micronuclei formation

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