TOP1 is 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. 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. TOP1 has been known as a target for the treatment of human cancers. Camptothecin analogues irinotecan and topotecan, which inhibit TOP1, are among the most effective FDA-approved anticancer chemotherapeutic agents used in clinical practice. Higher expression of TOP1 in KRAS mutant non-small cell lung cancer and correlation to survival suggests that TOP1 inhibitors might have increased benefit when administered to treat patients with a KRAS mutant tumor.
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