TOP1

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 allows the strands to pass through one another, thus altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22. [provided by RefSeq]

TOP1

Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity).
Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.

Biological Process chromatin remodeling Source:UniProtKB1 Publication
Biological Process chromosome segregation Source:GO_Central1 Publication
Biological Process circadian regulation of gene expression Source:UniProtKB1 Publication
Biological Process circadian rhythm Source:UniProtKB1 Publication
Biological Process DNA replication Source:GO_Central1 Publication
Biological Process DNA topological change Source:UniProtKB1 Publication
Biological Process embryonic cleavage Source:Ensembl
Biological Process peptidyl-serine phosphorylation Source:CAFA1 Publication
Biological Process phosphorylation Source:UniProtKB1 Publication
Biological Process programmed cell death Source:UniProtKB1 Publication
Biological Process response to xenobiotic stimulus Source:UniProtKB1 Publication

Nucleus, nucleolus
Nucleus, nucleoplasm
Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumoylated forms found in both nucleoplasm and nucleoli.

A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.

Sumoylated. Lys-117 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment.
Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin.