A Primase-Induced Conformational Switch Controls the Stability of the Bacterial Replisome

Enrico Monachino, Slobodan Jergic, Jacob S. Lewis, Zhi-Qiang Xu, Allen T.Y. Lo, Valerie L. O’Shea, James M. Berger, Nicholas E. Dixon, Antoine M. van Oijen

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Recent studies of bacterial DNA replication have led to a picture of the replisome as an entity that freely exchanges DNA polymerases and displays intermittent coupling between the helicase and polymerase(s). Challenging the textbook model of the polymerase holoenzyme acting as a stable complex coordinating the replisome, these observations suggest a role of the helicase as the central organizing hub. We show here that the molecular origin of this newly found plasticity lies in the 500-fold increase in strength of the interaction between the polymerase holoenzyme and the replicative helicase upon association of the primase with the replisome. By combining in vitro ensemble-averaged and single-molecule assays, we demonstrate that this conformational switch operates during replication and promotes recruitment of multiple holoenzymes at the fork. Our observations provide a molecular mechanism for polymerase exchange and offer a revised model for the replication reaction that emphasizes its stochasticity.
Original languageEnglish (US)
Pages (from-to)140-154.e7
Number of pages1539999861
JournalMolecular Cell
Issue number1
StatePublished - Jul 2020
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology


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