2. What will we discuss?
▪ Topoisomerases catalyze changes in the linking number of DNA
▪ Topoisomerase I
▪ Topoisomerase II
▪ What happens if there is no topoisomerase?
3. Topoisomerases Catalyze Changes
in the Linking Number of DNA
▪ All cells, from bacteria to eukaryotes, have enzymes with the sole
function of underwinding and relaxing DNA.
▪ Topoisomerases increase or decrease the extent of DNA
underwinding by changing the linking number.
▪ They play an especially important role in the complex changes in
DNA topology during replication and DNA packaging.
4. Topoisomerase I
▪ Type I enzymes breaks one of the two DNA strands
▪ The type I enzymes are called topoisomerases I and III
▪ They change Lk in increments of 1
▪ Remove negative supercoils (increasing Lk)
▪ Type I enzymes do not require any high-energy cofactor for activity;
the reaction is driven by the energy stored in the supercoiled DNA as
torsional strain
5.
6. Topoisomerase II
▪ Type II topoisomerases break both DNA strands
▪ The type II enzymes are topoisomerases Ila and IIb
▪ They change Lk in increments of 2
▪ Bacterial topoisomerase II, also known as DNA gyrase, can introduce
negative supercoils (decrease Lk)
▪ Type II enzymes utilize ATP hydrolysis to drive conformational
changes in the protein during the reaction cycle
7.
8. EukaryoticTopoisomerase II
▪ Eukaryotic type II topoisomerases cannot underwind DNA (introduce
negative supercoils), but they can relax both positive and
negative supercoils.
9.
10. What happens if there is no topoisomerase?
▪ Topoisomerase alleviates supercoiling downstream of the origin of
replication. In the absence of topoisomerase, supercoiling tension
would increase to the point where DNA could fragment.
▪ DNA replication will stop and leads to cell death
