Picropodophyllotoxin, IGF-1R inhibitor

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

Topoisomerase II alpha also known as TOP2A is an essential enzyme for DNA replication and transcription. It works by creating transient double-strand breaks in DNA molecules allowing the passage of another portion of DNA molecule through the break and then it re-ligates the broken strands. The correct function of TOP2A is critical for cell division as it helps in resolving DNA entanglements during processes such as mitosis. The enzyme typically has a mass around 170 kDa and sees robust expression in rapidly proliferating cells such as those found in tumors due to their high need for DNA replication.

Biological function summary

Topoisomerase II alpha serves an important role in the regulation of DNA topology through its enzymatic activity. It forms part of the DNA topoisomerase family which functions as an individual molecule rather than being part of a large protein complex. TOP2A is responsible for managing DNA supercoiling and untangling of chromosomes essential during both replication and transcription processes. Its function supports genomic stability and mutations can result in serious cellular abnormalities.

Pathways

Topoisomerase II alpha integrates into the DNA replication and repair pathways playing a significant role in ensuring the integrity of genetic information during cell division. It interacts closely with other proteins such as replication protein A (RPA) during DNA replication. Additionally TOP2A is also involved in the DNA damage response pathway where it helps resolve DNA supercoiling that might arise due to transcription and replication blockage.

TOP2A shows a strong connection to cancer most notably in types where cell proliferation is excessive such as breast cancer and lymphomas. Its overexpression has been linked with aggressive tumor development and resistance to chemotherapeutic drugs. Additionally TOP2A becomes a target for certain anti-cancer agents such as etoposide and podophyllotoxin which inhibit its activity and induce apoptosis in rapidly dividing cells. These drugs specifically exploit the enzyme's important role in DNA replication to exert anti-tumor effects highlighting TOP2A's role in oncology.