Topoisomerase II residues 409-1201 / NMR Structure of a 21 bp DNA duplex preferentially cleaved by

Human Topoisomerase II (10 conformations) / Structure of the Topoisomerase II poison bound to DNA

Nucleotides are the basic components of nucleic acids, including DNA and RNA. They are built on the association of a base, a sugar and phosphates. Combining six nitrogenous bases (A, C, G, T, U and H), two sugars (ribose and 2’-deoxyribose) and one to three phosphate groups leads to a large diversity of nucleic acids involved in many biological processes, as gene transmission.

Many mutagens fit into the space between two adjacent base pairs (intercalating agents). Most of these molecules are aromatic and planar and their presence prevents DNA to adopt its double helix structure, inhibiting transcription and replication, causing toxicity and mutations. These toxins can be used for therapeutic purposes in chemotherapy to stop the growing of cancer cells.

Many proteins have to recognize nucleotides during their biological action and have a specific site dedicated to this. Among others, kinases, phosphodiesterases, polymerases, reverse transcriptases and topoisomerases belong to this category. Nucleotide interacting molecules can block the function of these proteins in order to have an action on a specific biological pathway.