From cryo-EM structures to molecular mechanisms in DNA replication

Abstract

The assembly of replicative helicase onto DNA is central to the regulation of replication initiation. A family of six homologous subunits, Mcm2-7, forms the catalytic core of the eukaryotic replicative helicase. The necessity of six similar but non-identical subunits has been a mystery since its initial discovery. With the advent of the cryo-electron microscopy, we have solved a series of high-resolution structures of the complexes that are required for assembling Mcm2-7 complexes onto DNA. These structures include Origin Recognition Complex (Nature 2018), Mcm2-7, Cdt1-Mcm2-7 (Nat Struct Mol Biol 2017), and Mcm2-7 double hexamer (Nature 2015). The information derived from these structures provides significant insights into the unique roles of MCM subunits in orchestrating its own loading as well as the molecular mechanisms of replication initiation.