Origin firing

Cryo-electron microscopy structures of the sequential assembly of the CMG replicative helicase on a chromatinized origin of replication provide insights into the mechanism through which DNA melting is initiated by ATP binding.

In addition to CDC7, the cell cycle kinase CDK1 has a pivotal role in the G1/S transition of cells, a finding that revises our current understanding of cell cycle progression.

The Dbf4-dependent kinase Cdc7 (DDK) is essential for eukaryotic DNA replication. Here, the authors present a series of cryo-EM structures elucidating the versatility of this kinase in exerting an ordered phosphorylation of its essential target to promote replication initiation.

A cryo-EM structure of the Dbf4-dependent kinase (DDK) in the act of phosphorylating an Mcm2-7 helicase complex reveals how DDK selectively targets DNA-loaded MCM double hexamers to trigger replication origin activation. Checkpoint kinase Rad53 blocks origin firing by impairing double hexamer engagement by DDK.

In this Article, the authors identify CcrZ as a protein that coordinates DNA replication and cell division in Streptococcus pneumoniae and other Firmicutes. CcrZ is localized to the division site by binding directly to the divisome protein FtsZ, and there it activates DnaA, the master initiator of DNA replication, through a still unknown mechanism.

During pre-Replication Complex, eukaryotic cells load two MCMs into a head-to-head Double Hexamer around duplex DNA (DH). Here the authors preRC assembly assay with purified proteins to reveal insights into S. cerevisiae’s first steps that lead to the DH formation.