OKAZAKI FRAGMENTS Short fragments of newly synthesised DNA strands produced during DNA replication. All the known DNA polymerases can only synthesis DNA in one direction, the 5' to 3' direction. However as the strands separate, replication forks will be moving along one parental strand in the 3' to 5' direction and 5' to 3' on the other parental strand. On the former, the leading strand, DNA can be synthesised continuously in the 5' to 3' direction. On the other, the lagging strand, DNA synthesis can only occur when a stretch of single stranded DNA has been exposed and proceeds in the direction opposite to the movement of the replication fork (still 5' to 3). It is thus discontinuous and the series of fragments are then covalently linked by ligases to give a continuous strand. Such fragments were first observed by Okazaki using pulse labelling with radioactive thymidine. In eukaryotes, Okazaki fragments are typically a few hundred nucleotides long, whereas in prokaryotes they may contain several thousands of nucleotides The Okazaki fragments must then be joined together. This is performed by two enzymes, DNA polymerase I and DNA ligase. The leading strand grows in the 5' to 3' direction of the replication fork's movement while the lagging strand grows in the opposite direction to the replication fork. DNA polymerase I can function as a polymerase, a 3' to 5' exonuclease and a 5' to 3' exonuclease. The 5' to 3' exonuclease function destroys the RNA primer and the polymerase activity replaces the primer with DNA. DNA ligase creates phosphodiester boinds to join, or ligate the fragments together into a continuous strand. So the DNA Okazaki fragments still grow in a 5' to 3' direction, but overall the strand grows in a 3' to 5' direction as each fragment is ligated to the next one.