Doxorubicin hydrochloride, Topoisomerase II inhibitor

Supplementary information

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

Topoisomerase II alpha (TOP2A) TopBP1 and Topoisomerase II beta (TOP2B) are notable proteins that play essential roles in DNA metabolism. These enzymes function in resolving topological issues during DNA replication transcription and are vital for other cellular processes. TOP2A and TOP2B cleave and rejoin DNA strands to relieve torsional strain introduced during these activities. TOP2A has a mass of approximately 170 kDa and is expressed highly in proliferating cells. Meanwhile TOP2B shows broader expression patterns and remains expressed in non-dividing cells. TopBP1 known as a binding partner assists in the recruitment and regulation of these topoisomerases and links them to the checkpoint control pathways.

Biological function summary

These proteins are involved in maintaining genomic stability. TOP2A and TOP2B operate within complexes that ensure proper chromosomal segregation and repair DNA double-strand breaks. TopBP1 plays a pivotal role in activating DNA damage response particularly during replication stress by interacting with ATR kinase. This interaction facilitates the recognition and repair of damaged DNA. Such functions are critical for cell cycle progression and undisturbed chromosomal integrity impacting cellular responses to DNA damage.

Pathways

These proteins integrate into key cellular mechanisms like the cell cycle and DNA repair pathways. TOP2A and TOP2B through their DNA cleaving and rejoining actions interact closely with proteins like BRCA1 and RAD51 central to homologous recombination repair. TopBP1 participates in the ATR-Chk1 signaling pathway which coordinates cell cycle arrest and repair efforts post replication stress. These interactions ensure cells can stall their cycle to correct errors before proceeding with division providing a defense mechanism against potential threats to integrity and stability of the genome.

Aberrations in the activities of these proteins associate with cancer and neurological disorders. Elevated TOP2A expression is often observed in aggressive cancers where it correlates with genomic instability and tumor progression. Chemotherapeutic agents like 'doxorubicin' and 'dox hcl' target TOP2A to disrupt these cancer cells' proliferation. TOP2B mutations have linkage to neuropathies due to their role in non-dividing neuronal cells' maintenance. Alterations in TopBP1 can impede proper DNA damage response heightening the risk for cancers related to defective DNA repair sharing interactions with proteins like ATR which impair checkpoint controls.