TOP1

Description

The TOP1 (DNA topoisomerase I) is a protein-coding gene located on chromosome 20.

TOP1 is a human gene that encodes DNA topoisomerase 1, an enzyme responsible for controlling and altering the topology of DNA during transcription. It catalyzes the transient breaking and rejoining of a single DNA strand, allowing the broken strand to rotate around the intact strand, thus altering the topology of DNA. TOP1 is located on chromosome 20 and has pseudogenes on chromosomes 1 and 22. It belongs to the type IB topoisomerases, which form a covalent intermediate where the active site tyrosine becomes attached to the 3' phosphate end of the cleaved strand. TOP1 preferentially nicks DNA at a specific sequence (5'-(A/T)(G/C)(A/T)T-3'), with the enzyme covalently attached to the -1 T residue. The TOP1 protein is composed of four regions: an N-terminal domain, a conserved core domain containing catalytic residues, a linker domain, and a C-terminal domain. The N-terminal domain contains nuclear localization signals and sites for interaction with other proteins.

TOP1, also known as DNA topoisomerase I, is involved in releasing supercoiling and torsional tension in DNA that arises during replication and transcription. This is achieved through a transient cleaving and rejoining of one DNA strand. TOP1 introduces a single-strand break via transesterification at a specific site in the DNA duplex. The catalytic tyrosine of TOP1 attacks the phosphodiester bond, forming a covalent intermediate between TOP1 and the cleaved DNA strand. The 5'-OH end of the broken DNA strand is then released, allowing the free strand to rotate around the intact strand, thereby relieving supercoiling. Finally, the 5'-OH end of the broken strand attacks the covalent intermediate, expelling the tyrosine and restoring the DNA phosphodiester backbone. TOP1 also regulates alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and is involved in the circadian transcription of the BMAL1 gene by influencing chromatin structure around ROR response elements (ROREs) on the BMAL1 promoter.

TOP1 is also known as TOPI.

Associated Diseases

WES Whole Exome Sequencing