ICL in biology refers to Interstrand Crosslinks, which are cytotoxic DNA lesions.
In more detail:
Interstrand Crosslinks (ICLs) are damaging covalent bonds that link the two complementary strands of a DNA double helix. This crosslinking prevents DNA strand separation, which is crucial for processes like DNA replication, transcription, and DNA repair. Because of their ability to block these essential cellular processes, ICLs are highly toxic to cells.
ICLs can arise from:
- Exogenous sources: Certain chemotherapeutic drugs, such as cisplatin and mitomycin C, are designed to induce ICLs in cancer cells, thereby inhibiting their proliferation.
- Endogenous sources: Malondialdehyde, a product of lipid peroxidation, has been suggested as an endogenous source, forming DNA adducts that rearrange into ICLs.
The repair of ICLs is complex and primarily involves the Fanconi anemia (FA) pathway, a crucial DNA repair mechanism. Defects in this pathway can lead to increased sensitivity to ICL-inducing agents and can cause diseases like Fanconi anemia, a rare genetic disorder characterized by bone marrow failure, developmental abnormalities, and an increased risk of cancer.
