DNA polymerases at the replication fork in eukaryotes

Abstract

The Kunkel laboratory has recently assigned polymerase (Pol) epsilon as the leading strand polymerase. In a recent issue of Molecular Cell, they now assign Pol delta as the lagging strand polymerase.

Figure

Left panel: DNA replication fork showing the proteins that are required for replication of SV40 DNA. The SV40 T antigen functions to recruit polymerase α/primase and also as a DNA helicase to unwind the DNA. Primers made by polymerase α/primase are then recognized by RFC and PCNA to load polymerase δ that completes the Okazaki fragments on the lagging strand. Polymerase δ also synthesizes the leading strand. Right panel: Replication forks that emerge from cellular origins of DNA replication are established by priming by polymerase α/primase priming, but in this case polymerase ε synthesizes the leading strand and polymerase δ the lagging strand. Instead of T antigen to unwind the DNA, helicase activity is provided by the Cdc45-MCM-GINS (CMG) complex. Polymerase δ is activated by the PCNA polymerase clamp, but whether this occurs on the leading strand for polymerase ε remains to be determined. How polymerase ε is loaded is under investigation.