An archaeal order with multiple minichromosome maintenance genes

Abstract

In eukaryotes, a complex of six highly related minichromosome maintenance (MCM) proteins is believed to function as the replicative helicase. Until recently, systems for exploring the molecular mechanisms underlying eukaryotic MCM function have been biochemically intractable. To overcome this, molecular studies of MCM function have been carried out using MCM homologues from the archaea. Archaeal MCM systems studied to date possess a single functional MCM, which forms a homohexameric complex that displays DNA binding, ATPase and helicase activities. We have identified an archaeal order that possesses multiple MCM homologues. blast searches of available Methanococcales genomes reveal that members of this order possess between two and eight MCM homologues. Phylogenetic analysis suggests that an ancient duplication in the Methanococcales gave rise to two major groups of MCMs. One group contains Methanococcus maripaludis S2 McmD and possesses a conserved C-terminal insert similar to one observed in eukaryotic MCM3, while the other group contains McmA, -B and -C. Analysis of the genome context of MCMs in the latter group indicates that these genes could have arisen from phage-mediated events. When co-expressed in Escherichia coli, the four MCMs from M. maripaludis co-purify, indicating the formation of heteromeric complexes in vitro. The presence of homologues from both groups in all Methanococcales indicates that there could be functionally important differences between these proteins and that Methanococcales MCMs may therefore provide an interesting additional model for eukaryotic MCM function.