DNA synthesis interference

“DNA synthesis interference” refers broadly to any disruption—by chemical agents, genetic mutations, metabolic imbalances,[2] or regulatory mechanisms—of the normal process by which cells replicate their genomic material before division. This can occur through direct inhibition at origins of replication (“origin interference”)[1], depletion/misincorporation of nucleotide precursors,[2] inhibition/destruction/inactivation of essential proteins such as polymerases,[4][5] helicases,[4], topoisomerases,[4], primase[5], ligase[5], etc., or through checkpoint signaling pathways that halt S phase progression when errors are detected.[3] While intentional induction forms the basis for many anticancer therapies targeting rapidly dividing tumor cells via cytotoxicity from failed genome duplication,[2] unintentional disruption underlies various disease states characterized by genomic instability.

Other names

Inhibition of DNA replicationReplication origin interferenceDNA replication stress

Mechanisms by which drugs interfere with DNA synthesis include: Inhibiting nucleotide biosynthesis, incorporating faulty nucleotides into replicating DNA, and blocking activity of key enzymes like topoisomerases and polymerases. These actions result in stalled replication forks, double-strand breaks, and ultimately cell death if damage is irreparable.