TOP1
GeneName
TOP1
Summary
TOP1, also known as topoisomerase I or DNA topoisomerase I, is a 91 kDa nuclear enzyme that plays a vital role in DNA metabolism by introducing single-strand breaks in DNA to alleviate torsional strain during processes such as DNA replication and transcription. It is primarily localised in the nucleus and nucleolus, where it interacts with chromatin and various protein-DNA complexes. TOP1 is involved in chromatin remodelling and is essential for chromosome segregation, DNA replication, and the regulation of gene expression. Its activity is ATP-independent and includes binding to supercoiled and single-stranded DNA, as well as RNA binding capabilities.
Importance
TOP1 is relevant to: - Cancer research, as it is a target for chemotherapeutic agents like camptothecin that inhibit its activity, leading to DNA damage in rapidly dividing cells. - Studies of DNA repair mechanisms and the cellular response to DNA damage, which are crucial for understanding genomic stability. - Regenerative medicine, given its role in animal organ regeneration and cellular responses to various stimuli. - Circadian biology, due to its involvement in the circadian regulation of gene expression and response to environmental signals.
Top Products
For researchers investigating TOP1, we highly recommend the top-selling recombinant antibody, Anti-Topoisomerase I antibody [EPR5375] (ab109374). This antibody has been validated in various applications, including Western blotting (WB), immunocytochemistry (ICC), immunohistochemistry (IHC), and flow cytometry (FC), making it a versatile tool for your research needs. With 56 citations, it is well-regarded in the scientific community, demonstrating its reliability and effectiveness in TOP1 detection. This product offers the consistency and performance that researchers seek in their studies.
Abcam Product Citation Summary
The data indicates that the TOP1 antibody (ab109374) has been primarily used in Western blot analyses across various species, including rats and human cell lines. The studies focus on the effects of BPA treatment and DNA double-strand breaks, highlighting the relevance of TOP1 in cellular responses to DNA damage and repair mechanisms.
Abcam Product Citation Table
Function
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 BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter.
Involvement in disease
A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.
Post-translational modifications
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.
Sequence Similarities
Belongs to the type IB topoisomerase family.
Tissue Specificity
Endothelial cells.
Cellular localization
- 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.
Alternative names
DNA topoisomerase 1, DNA topoisomerase I, TOP1