Molecular Classification
Other
Other Names
DNA interstrand crosslink, DNA intrastrand crosslink, DNA-protein crosslink, ICL (interstrand crosslink)
Disease Roles
Cancer (as a therapeutic target/process)

DNA crosslink Overview

DNA crosslinks are covalent bonds formed between two nucleotides within the same strand (intrastrand) or across opposite strands (interstrand) of double-stranded DNA. These lesions can be caused by exogenous agents such as chemotherapeutic drugs (e.g., cisplatin, melphalan, mitomycin C), environmental toxins, or endogenous metabolic products. Crosslinks block essential cellular processes like replication and transcription; if unrepaired, they trigger cell death through apoptosis. This property is exploited in cancer chemotherapy to selectively kill rapidly dividing tumor cells. However, the process itself is not a discrete molecular target such as a receptor or enzyme but rather a type of chemical damage induced in the genome[2][4]. Therefore, "DNA crosslinking causing apoptosis" describes a mechanism or effect rather than an individual molecular entity that can be directly targeted by drugs. **Note:** There is something incorrect with this entry as it refers to a process/mechanism ("DNA crosslinking causing apoptosis") rather than an individual molecule/receptor/target protein. The canonical form should refer to specific enzymes involved in repair pathways or specific drug targets that induce this effect—not the process itself[2][4].

Mechanism of Action

Induction of apoptosis via inhibition of DNA replication and transcription by covalent linkage between nucleotides[2][4]

Biological Functions

Cell death
Apoptosis
Inhibition of DNA replication and transcription

Disease Associations

Cancer (as a therapeutic target/process)

Safety Considerations

  • Off-target cytotoxicity to healthy cells[1][3]

Interacting Drugs

Cisplatin
Melphalan
Nitrogen mustard (HN2)
Mitomycin C (MMC)[3][4]