Gosset DNA Strand Crosslinking 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.
Mechanism of Action
Formation of covalent linkages within or between DNA strands, leading to replication and transcription stalling, and ultimately cell death if unrepaired.
Biological Functions
Disease Associations
Safety Considerations
- Hypersensitivity reactions to crosslinking agents
- Development of resistance to chemotherapeutic agents
- Secondary malignancies due to DNA damage