Leading & Lagging Synthesis

Simultaneous DNA synthesis on leading & lagging strands

DNAPol III is a dimeric holoenzyme that synthesizes both the leading and lagging strands simultaneously. The process occurs consistent with the requirement that new strand synthesis always occurs 5'3'.

In the upper diagram, the leading strand passes through the polymerase subunit in the 5'3' direction 'right to left', such that synthesis off the leading strand in the 5'3' direction occurs continuously towards the replication fork. Simultaneously, the lagging strand passes through the alternate polymerase subunit, also in the 5'3' direction, but in order to do so must enter it in the opposite orientation. This effectively reverses the "left-right" orientation of 5'3' synthesis off the lagging strand: both blue arrows in the upper diagram are oriented 'left to right'.

Now, imagine rotating the lower polymerse subunit in the upper diagram 180^o to the left (lower diagram) so that both are in the same orientation. The leading and lagging strands now both pass through the dimeric subunits 'left to right' but in opposite 5'3' directions, and that lagging strand synthesis is directed away from the replication fork, as a series of short Okazaki fragments.