Crosslinking of DNA

Exogenous crosslinking agents are chemicals and compounds, both natural and synthetic, that stem from environmental exposures such as pharmaceuticals and cigarette smoke or automotive exhaust.

Endogenous crosslinking agents are compounds and metabolites that are introduced from cellular or biochemical pathways within a cell or organism.

The Werner syndrome (WRN) helicase and the BRCA1 protein collaborate as part of a cellular response to repair DNA interstrand crosslinks.

[citation needed] Once pairing has occurred, the crosslink can be removed and correct information introduced into the damaged chromosome by homologous recombination.

[20] in vitro evidence demonstrated that the Interstand Cross-Links induced by abasic site (DOB-ICL) is a replication-blocking and highly miscoding lesion.

The advancement in structure-identification methods has progressed, and the addition in the ability to measure interactions between DNA and protein is a requirement to fully understand the biochemical processes.

These cross-linking agents have the ability to act as single-agent therapies by targeting and destroying specific nucleotides in cancerous cells.

This result is stopping the cycle and growth of cancer cells; because it inhibits specific DNA repair pathways, this approach has a potential advantage in having fewer side effects.

[29] Individuals with NSCLC are often treated with therapeutic platinum compounds (e.g. cisplatin, carboplatin or oxaliplatin) (see Lung cancer chemotherapy) that cause interstrand DNA crosslinks.

Among individuals with NSLC, low expression of the breast cancer 1 gene (BRCA1) in the primary tumor has correlated with improved survival after platinum-containing chemotherapy.

High BRCA1 may protect cancer cells by acting in the homologous recombinational repair pathway that removes the damages in DNA introduced by the platinum drugs.

Crosslinking is also possible in other therapeutic agents by either stabilizing covalent DNA–protein reaction intermediates or by creating a pseudosubstrate, which traps the enzyme on DNA.