DNA Topoisomerases

The unwinding of the DNA double helix during replication results in overwinding in regions ahead of the replication fork. 

Additionally, supercoiling can occur when the DNA twists back on itself due to the inability of the DNA ends to freely rotate to relieve the torsional stress. This twisting inhibits further unwinding of the DNA, stalling vital cell processes such as DNA replication. 

To deal with this winding problem, cells have enzymes known as topoisomerases that have both nuclease and ligase activity; that is, these enzymes reversibly break then reconnect phosphodiester bonds in DNA to remove torsional strain in overwound DNA.

Topoisomerases fall into two categories. 

Type I topoisomerases are ATP-independent and act by cutting a bond between nucleotides on a single strand of double stranded DNA. 

The unbroken DNA strand is then passed through the gap in the broken strand into the upper cavity of the enzyme. 

Finally, the enzyme ligates the broken ends of the DNA strands back together and produces a locally relaxed DNA molecule.

Type II topoisomerases, on the other hand, are ATP-dependent and act on supercoiled DNA where the DNA is tangled around itself. 

The enzyme creates a double strand break in one loop of the DNA double helix before helping the unbroken loop to pass through this break via an ATP-dependent reaction.

Then, using the energy from a second ATP, Type II topoisomerase reseals the broken ends of the DNA strands and finally detaches from the DNA- leaving behind an untangled DNA helix.