DNA topoisomerase 1 is an enzyme that in humans is encoded by the TOP1 gene. It is a DNA topoisomerase, an enzyme that catalyzes the transient breaking and rejoining of a single strand of DNA. Function This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which lets the broken strand rotate around the intact strand, thus altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22. Mechanism As reviewed by Champoux, the type IB topoisomerases, including TOP1, form a covalent intermediate in which the active site tyrosine becomes attached to the 3' phosphate end of the cleaved strand rather than the 5' phosphate end. The eukaryotic topoisomerases I were found to nick the DNA with a preference for a sequence of nucleotides that extends from positions -4 to -1 from the nick. The preferred nucleotides in the strand to be cut are 5'-(A/T)(G/C)(A/T)T-3' with the enzyme covalently attached to the -1 T residue, though sometimes a C residue is found at the -1 position. The TOP1 protein of humans has been subdivided into four regions. The N-terminal 214 amino acids are dispensable for relaxation of supercoiling activity in vitro and there are four nuclear localization signals and sites for interaction with other cellular proteins within the N-terminal domain. The N-terminal domain is followed by a highly conserved, 421 amino acid core domain containing all of the catalytic residues except the active site tyrosine. This is followed by a poorly conserved linker domain of 77 amino acids. Finally there is a 53 amino acid C-terminal domain. The active site Tyr723 is found within the C-terminal domain. As further summarized by Pommier and by Seol et al., TOP1 breaks the DNA by a transesterification reaction using the active site tyrosine as the nucleophile that attacks the DNA phosphodiester backbone. After the TOP1 covalently attaches to the 3' end of the broken strand, supercoiling of the DNA is relaxed by controlled rotation of DNA about the intact strand. Then the 5' hydroxyl end of the broken DNA strand can reverse the phosphotyrosyl bond, enabling the release of TOP1 and religation of the DNA. The nicking and closing reactions are fast, and about 100 cycles can occur per