MoBio Topoisomerase Chapter 7

During replication, the unwinding of DNA may cause the formation of tangling structures, such as supercoils or catenanes. The major role of topoisomerases is to prevent DNA tangling.

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Figure 7-D-1. Structure of the Topo I/DNA complex. PDB ID = 1A36.

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Figure 7-D-2. The structure of supercoils. (a) Positive supercoils - the front segment of a DNA molecule cross over the back segment from left to right. (b) Negative supercoils. (c) The positive supercoil in bacteria during DNA replication.

There are two types of topoisomerases: type I produces transient single-strand breaks in DNA and types II produces transient double-strand breaks. As a result, the type I enzyme removes supercoils from DNA one at a time, whereas the type II enzyme removes supercoils two at a time. Although the type II topoisomerase is more efficient in removing supercoils, this enzyme requires the energy from ATP hydrolysis, but the type I topoisomerase does not.

The topo I of both prokaryotes and eukaryotes are the type I topoisomerase. The eukaryotic topo II, bacterial gyrase, and bacterial topo IV belong to the type II.

In eukaryotes, the topo I and topo II can remove both positive and negative supercoils.

In bacteria, the topo I can remove only negative supercoils. The bacterial topo II is also called the gyrase, which has two functions: (1) to remove the positive supercoils during DNA replication, (2) to introduce negative supercoils (one supercoil for 15-20 turns of the DNA helix) so that the DNA molecule can be packed into the cell. During replication, these negative supercoils are removed by topo I.

The bacterial topo IV belongs to the type II topoisomerase. This enzyme is involved in decatenation.

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Figure 7-D-3. The function of topo II:
(a) To remove supercoils. This involves a double-strand break (indicated by a short line), allowing the tangled segment to pass through. The break is then resealed.
(b) To remove catenanes. The topo II makes a double-strand break in one DNA molecule (the blue one), allowing the other molecule to pass through. The break is then resealed.

Without topoisomerases, the DNA cannot replicate normally. Therefore, the inhibitors of topoisomerases have been used as anti-cancer drugs to stop the proliferation of malignant cells. However, these inhibitors may also stop the division of normal cells. Some cells (e.g., hair cells) which need to continuously divide will be most affected. This explains a noticeable side effect: the hair loss.