- DNA is tightly packed inside of the nucleus
- topoisomerase untangles and relaxes DNA strands
- Class I topoisomerases solve the problem of the tension caused during the winding and unwinding of DNA. One example is shown here from PDB entry 1a36 . It wraps around the DNA and makes a cut in one strand (through a tyrosine residue). Then, while holding onto the damaged spot, the enzyme allows the helix to spin, releasing any overwinding or underwinding. Once the DNA is relaxed, the topoisomerase reconnects the broken strand, restoring the DNA double helix.
- Class II topoisomerases specialize in untangling DNA in the nucleus. For instance, when a cell is dividing, it needs to separate the two copies of each chromosome. During this process, portions of the two sister chromosomes may become looped around each other, getting hung up together as they are separated. Class II topoisomerase solves this problem by allowing one DNA helix to pass through the other one. It cuts both strands of one DNA double helix, keeping a firm grip on both halves. Then, it passes the other DNA through the gap, resolving the tangle. Finally, it reattaches the broken ends, restoring the DNA.
[[camptothecin]], [[doxorubicine]], daunorubicine
- How many nucleotides are there in a human genome?
- What is the size of the nucleus?
- Describe mechanism of tyrosine-catalyzed phosphodiester cleavage by topoisomerase.