Type I topoisomerase

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Topoisomerase I solves the problem caused by tension generated by winding/unwinding of DNA. It wraps around DNA and makes a cut permitting the helix to spin. Once DNA is relaxed, topoisomerase reconnects broken strands (PDB code=1a36)

Type I topoisomerases function by nicking one of the strands of the DNA double helix, twisting it around the other strand, and re-ligating the nicked strand.

This is not an active process in the sense that energy in the form of ATP is not spent during the nicking or ligation steps as the reaction between the tyrosine residue at the active site of the enzyme with the phosphodiester DNA backbone simply replaces one phosphomonoester bond with another. The topoisomerase also does not use ATP during uncoiling of the DNA; rather, the torque present in the DNA drives the uncoiling.

Classification

Type I enzymes can be further subdivided into type IA and type IB, based on their chemistry of action.

• Type IA topoisomerases change the linking number of a circular DNA strand by units of strictly 1.
• Type IB topoisomerases change the linking number by multiples of 1.

Prokaryotic topoisomerase I can only relax negative supercoiling, whereas eukaryotic topoisomerase I can affect both negative and positive supercoiling. These variants of topoI are not evolutionarily related.

Intermediates

All topoisomerases form a phosphotyrosine intermediate between the catalytic tyrosine of the enzyme and the scissile phosphoryl of the DNA backbone.

• Type IA topoisomerases form a covalent linkage between the catalytic tyrosine and the 5'-phosphoryl.
• Type IB enzymes form a covalent 3'-phosphotyrosine intermediate.

Diversity

Apart from these similarities, they have very different mechanisms of action, have different crystal structures and appear not to have similar evolutionary ancestors.

Inhibition

Type 1 topoisomerase is inhibited by irinotecan, topotecan and camptothecin.

External links

• MeSH DNA+Topoisomerases,+Type+I