Look Ma, no PCNA: how DNA polymerase ? synthesizes long stretches of DNA without a processivity factor

摘要

Despite their opposite polarity, the two antiparallel strands of the DNA double helix are synthesized concomitantly as the replication fork translocates in a single direction. Given that the vast majority of DNA polymerases add nucleotides exclusively to the 3' terminus, nature has devised a strategy of discontinuous synthesis in the 3'-to-5' direction, whereby short RNA primers are extended and the resulting DNA segments ligated to form the nascent lagging strand. It is therefore not surprising that evolution has selected for specialized DNA polymerases that make distinct contributions to leading- and lagging-strand synthesis. Three B-family DNA polymerases (α, δ and ε) comprise the eukaryotic replisome, and the latter two bear the primary responsibility of synthesizing most of the DNA in dividing cells. In yeast, DNA polymerase δ is believed to synthesize the lagging strand, while DNA polymerase ε extends the leading strand. In this issue, Johansson and colleagues unveil the first crystal structure of DNA polymerase ε at 2.2-? resolution (ref. 3), providing the companion structure required for comparison to polymerase δ, for which structural information is already available for both the catalytic domain and regulatory subunits. Importantly, the new structural data explain why, unlike polymerase δ, polymerase ε does not rely on the PCNA (proliferating cell nuclear antigen) sliding clamp for its high processivity.