Target intelligence / Profile preview

DNA Strand Crosslinking

Molecular classification
DNA Modification, Lesion
01

Overview

DNA strand crosslinking refers to the formation of covalent bonds between two nucleotides within DNA, either on the same strand (intrastrand) or between opposite strands (interstrand). These crosslinks can be induced by various exogenous agents or endogenous processes. Interstrand crosslinks (ICLs) are particularly cytotoxic as they block essential processes like replication and transcription. Many anticancer drugs function by inducing DNA crosslinks to kill rapidly dividing cells. Defects in pathways repairing interstrand crosslinks cause hypersensitivity to these lesions and underlie genetic disorders such as Fanconi anemia.

Other names
DNA CrosslinksInterstrand Crosslink (ICL)Intrastrand Crosslink
02

Mechanism of action

Formation of covalent linkages within or between DNA strands, leading to replication and transcription stalling, and ultimately cell death if unrepaired.

03

Biological functions

Blocks replicationBlocks transcriptionTriggers apoptosis (if unrepaired)DNA damage response
04

Disease associations

CancerFanconi AnemiaWerner SyndromeGenomic Instability
05

Safety considerations

Hypersensitivity reactions to crosslinking agentsDevelopment of resistance to chemotherapeutic agentsSecondary malignancies due to DNA damage
06

Interacting drugs

Cisplatin

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