The minichromosome maintenance protein complex (MCM) is a DNA helicase essential for genomic DNA replication. Eukaryotic MCM consists of six gene products, Mcm2–7, which form a heterohexamer. As a critical protein for cell division, MCM is also the target of various checkpoint pathways, such as the S-phase entry and S-phase arrest checkpoints. Both the loading and activation of MCM helicase are strictly regulated and are coupled to cell growth cycles. Deregulation of MCM function has been linked to genomic instability and a variety of carcinomas. History and structure The minichromosome maintenance proteins were named after a yeast genetics screen for mutants defective in the regulation of DNA replication initiation. The rationale behind this screen was that if replication origins were regulated in a manner analogous to transcription promoters, where transcriptional regulators showed promoter specificity, then replication regulators should also show origin specificity. Since eukaryotic chromosomes contain multiple replication origins and the plasmids contain only one, a slight defect in these regulators would have a dramatic effect on the replication of plasmids but little effect on chromosomes. In this screen, mutants conditional for plasmid loss were identified. In a secondary screen, these conditional mutants were selected for defects in plasmid maintenance against a collection of plasmids each carrying a different origin sequence. Two classes of mcm mutants were identified: Those that affected the stability of all minichromosomes and others that affected the stability of only a subset of the minichromosomes. The former were mutants defective in chromosome segregation such as mcm16, mcm20 and mcm21. Among the latter class of origin-specific mutants were mcm1, mcm2, mcm3, mcm5 and mcm10. Later on, others identified Mcm4, Mcm6 and Mcm7 in yeasts and other eukaryotes based on homology to Mcm2p, Mcm3p and Mcm5p expanding the MCM family to six, subsequently known as the Mcm2-7 family. In archaea, the heterohexamer ring is replaced by a homohexamer made up of a single type mcm protein, pointing at a history of gene duplication and diversification. Mcm1 and Mcm10 are also involved in DNA replication, directly or indirectly, but have no sequence homology to the Mcm2-7 family. Function in DNA replication initiation and elongation MCM2-7 is required for both DNA replication initiation and elongation; its regulation at each stage is a central feature of eukaryotic DNA replication. During G1 phase, the two head-to-head Mcm2-7 rings serve as the scaffold for the assembly of the bidirectional replication initiation complexes at