Fundamental steps in Minichromosome Maintenance complex assembly are conserved from archaea to eukaryotes

Abstract

Minichromosome maintenance (MCM) proteins are the replicative helicase in both archaea and eukaryotes. Recent cryo-EM studies have defined key steps in the assembly pathway of the eukaryotic MCM2-7 complex and determined roles for each subunit. While archaeal MCMs are simpler in composition, we know little about how these homohexameric MCMs assemble. Investigation of archaeal MCMs has largely focussed on proteins from thermophilic organisms, which typically form robust oligomers under ambient experimental conditions, preventing dissection of their assembly pathway. Here, we describe an uncharacterised MCM from the mesophilic archaeon Mancarchaeum acidophilum (MacMCM). A 3D structure of MacMCM reveals subunit-subunit interfaces that are more similar to yeast MCM2-7 than previously studied MCMs from thermophilic archaea. We show that assembly of a MacMCM homohexamer on DNA proceeds via comparable steps to MCM2-7. These results reveal an ancient mechanism underlies assembly of the MCM complex, which is conserved from archaea to eukaryotes.