Anti-Topoisomerase I-DNA Coval

Topoisomerase I-DNA covalent complexes are intermediate structures formed during the action of topoisomerase I, an essential enzyme involved in DNA replication, transcription, and recombination. Topoisomerase I works by introducing temporary single-strand breaks into the DNA backbone to relieve torsional strain caused by DNA unwinding. This allows the DNA to be untwisted, preventing supercoiling that could hinder the replication and transcription processes. After the relaxation, the enzyme re-ligates the break, leaving no permanent damage to the DNA. The covalent complex forms when topoisomerase I temporarily binds to the DNA through a covalent bond between its active site tyrosine and the DNA backbone. These complexes are key intermediates in the enzyme’s catalytic cycle. However, if the enzyme fails to reseal the break, the complex can become toxic, potentially leading to DNA damage, mutagenesis, or cell death, making the regulation of topoisomerase I activity critical for maintaining genome stability. These complexes are also targets for chemotherapeutic drugs, such as camptothecin, which inhibit the resealing of DNA breaks, inducing DNA damage in cancer cells.