DNA Synthesis (via platinum-DNA adducts)

DNA synthesis via platinum-DNA adducts refers to the process by which platinum-based compounds interact with DNA to form covalent adducts. These adducts disrupt normal DNA replication and transcription, leading to cytotoxic effects that are exploited in cancer chemotherapy. The primary binding sites are the N7 atoms on guanine and adenine, forming intrastrand and interstrand crosslinks, as well as monofunctional adducts. The bulky nature of these adducts blocks progression of both RNA polymerase II during transcription and various DNA polymerases during replication, ultimately inducing apoptosis if unrepaired.

Platinum-based drugs form covalent adducts with DNA, primarily at the N7 position of purine bases (guanine and adenine). These adducts distort the DNA double helix, blocking DNA replication and transcription, leading to cell cycle arrest and apoptosis in rapidly proliferating cells.