TOP1 Antibodies

Background

TOP1 is a key helicase widely present in the nucleus of eukaryotes. It regulates superhelical tension by reversibly cutting and reconnecting single DNA strands, ensuring the normal operation of core life processes such as DNA replication, transcription, and chromosome separation. Cancer cells are highly dependent on the activity of this enzyme due to their rapid proliferation characteristics, which makes TOP1 an important target for anti-tumor drugs (such as camptothecin-based preparations). In 1971, James Wang first discovered the activity of this enzyme in Escherichia coli. In 1987, the team led by Chinese scientist Wang Zhuo successfully analyzed its crystal structure and revealed a unique "rotary gate" catalytic mechanism - the enzyme molecule forms a covalent intermediate with DNA phosphodiester bonds through tyrosine residues, completing the topoisomerization reaction. As a model enzyme in the field of nucleic acid manipulation, the TOP1 study not only clarified the molecular basis for the dynamic maintenance of DNA, but also provided a theoretical framework for the development of new anti-cancer drugs and the understanding of the mechanism for maintaining genomic stability.

Structure Function Application Advantage Our Products

Structure of TOP1

TOP1 is a ribozyme with a molecular weight of approximately 91 kDa, and its precise molecular weight varies slightly among different species:

Species	Human	Mice	Bovine	Yeast
Molecular Weight (kDa)	90.7	89.2	91.3	85.6
Primary Structural Differences	Containing 765 amino acids, C end structure domain is longer than the other	Highly homologous to humans	Conservative catalytic core	Relatively simple structure

The unique "revolving door" mechanism enables it to instantly cut single-stranded DNA and reconnect after releasing helical tension through the tyrosine-phosphodiester bond covalent intermediate. This enzyme exhibits optimal activity under pH7.4 conditions. Mg²⁺ can enhance its stability, while camptothecin compounds can specifically capture the enzyme-DNA complex.

Fig. 1:Changes in the structure of TOP1. (OA Literature) Fig. 1 Domains composition of type IB topoisomerases.¹

Key structural properties of TOP1:

Characteristic "clip - core - connection zone" three-level structure
Conservative catalytic core domain
Unique "revolving door" mechanism
Metal ion-dependent activity regulation
Drug targeting sites of action

Functions of TOP1

The main function of TOP1 is to regulate the topological structure of DNA and play a key role in various cellular processes:

Function	Description
DNA superhelix relaxation	By reversibly cutting and reconnecting DNA single strands, the superhelical tension generated during replication and transcription is eliminated.
Regulation of gene expression	Maintain the open state of chromatin and promote the binding of transcription factors to DNA.
Maintenance of genomic stability	Prevent DNA from breaking due to excessive entanglement and ensure accurate chromosome separation.
Cell cycle regulation	The activity significantly increased in the S phase and G2 phase, supporting DNA replication and damage repair.
Anti-cancer drug targets	Forms stable complexes with camptothecin compounds to induce apoptosis of cancer cells (e.g., irinotecan, topotecan).

The catalytic efficiency of TOP1 shows a typical "ph-dependent" pattern, with the highest activity at a physiological pH of 7.4. Mg²⁺ can increase its activity by 3 to 5 times. Unlike type II topoisomerases, TOP1 only alters the number of DNA connections by ±1 each time it catalyzes. This precise regulation makes it a key molecule for maintaining genomic integrity.

Applications of TOP1 and TOP1 Antibody in Literature

1. Takahashi, Diane T., et al. "Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states." Nature communications 13.1 (2022): 59.https://doi.org/10.1038/s41467-021-27686-7

The apo structure of archaeal thermally stable topoisomerase I (CsTOP1) reveals that it mediates the rotation of CAP and CAT modules through hinge regions, forming an open conformation to allow DNA entry and exit. Conserved tyrosine regulates conformational transformation during DNA binding, and hinge flexibility affects the sensitivity of the anti-cancer drug camptothecin.

2. Xu, Yang, and Chengtao Her. "Inhibition of topoisomerase (DNA) I (TOP1): DNA damage repair and anticancer therapy." Biomolecules 5.3 (2015): 1652-1670. https://doi.org/10.3390/biom5031652

Research has found that topoisomerase I (TOP1) inhibitors selectively kill rapidly proliferating cancer cells by hindering DNA replication. This article explores the characteristics of TOP1, the mechanism of action of its inhibitors, related DNA repair pathways, and its application in cancer treatment.

3. Marini, Victoria, et al. "MUS81 cleaves TOP1-derived lesions and other DNA–protein cross-links." BMC biology 21.1 (2023): 110. https://doi.org/10.1186/s12915-023-01614-1

Research has found that structure-specific endonuclease MUS81 can clet various protein-DNA cross-links (DPCs), but it can only function after the TOP1 part is degraded. MUS81 and TDP1 independently repair the damage induced by TOP1 inhibitors, and their synergistic absence enhances the sensitivity of cells to camptothecin, providing a new target for the combination of TOP1 inhibitors in anti-cancer treatment.

4. Zhang, Huimin, et al. "TDP1-independent pathways in the process and repair of TOP1-induced DNA damage." Nature communications 13.1 (2022): 4240. https://doi.org/10.1038/s41467-022-31801-7

Research has found that the TOP1-DNA crossover (TOP1cc) induced by the anti-cancer drug camptosine (CPT) can be directly repaired by TDP1 or converted into double-strand breaks (DSBs) by MUS81 and then repaired through the homologous recombination (HR) pathway. Genome-wide CRISPR screening revealed that APEX1/2 and TDP1 have synthetic lethal effects, but APEX deficiency does not affect the formation of DSBs in TDP1-deficient cells, indicating that there are two independent repair pathways for TOP1cc.

5. Rubio-Contreras, Diana, and Fernando Gómez-Herreros. "TDP1 suppresses chromosomal translocations and cell death induced by abortive TOP1 activity during gene transcription." Nature Communications 14.1 (2023): 6940. https://doi.org/10.1038/s41467-023-42622-7

Research reveals that DNA breaks mediated by TOP1 can be repaired by TDP1 or transformed into double-strand breaks (DSBs), which in turn trigger genomic rearrangements through MRN complexes and fault-prone non-homologous end junctions. This discovery clarifies the crucial role of TDP1-dependent repair mechanisms in maintaining transcriptional and genomic stability.

Creative Biolabs: TOP1 Antibodies for Research

Creative Biolabs specializes in the production of high-quality TOP1 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom TOP1 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our TOP1 antibodies, custom preparations, or technical support, contact us at email.

Reference

Takahashi, Diane T., et al. "Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states." Nature communications 13.1 (2022): 59.https://doi.org/10.1038/s41467-021-27686-7