Molecular Classification
DNA, DNA Modification, Other
Other Names
DNA Alkylation, DNA Adduct Formation, Interstrand Crosslinks, Intrastrand Crosslinks, DNA Damage by Alkylating Agents
Disease Roles
Cancer

DNA Crosslinking via Alkylation Overview

DNA crosslinking via alkylation refers to the formation of covalent bonds between two nucleotides in DNA by alkylating agents, creating intra- or interstrand crosslinks. This process disrupts replication and transcription, leading to cell death and is exploited by many chemotherapeutic drugs. Repair mechanisms exist but can be overwhelmed, leading to mutations. The specific sequences targeted and the resulting DNA adducts vary depending on the alkylating agent.

Mechanism of Action

Covalent modification of DNA bases leading to interstrand or intrastrand crosslinks, inhibiting replication and transcription.

Biological Functions

Replication Inhibition
Transcription Inhibition
DNA Damage
Cell Death
Apoptosis

Disease Associations

Cancer

Safety Considerations

  • Mutagenesis
  • Secondary malignancies
  • Therapeutic resistance
  • Off-target effects

Interacting Drugs

Cyclophosphamide
Mitomycin C
Cisplatin
Nitrogen Mustards
Benzoquinones