MCM6

MCM6, or minichromosome maintenance complex component 6, is a protein-coding gene in humans that encodes a member of the MCM2-7 family of replicative helicases. The MCM2-7 complex forms a hexameric ring that unwinds double-stranded DNA at replication origins, providing the single-stranded templates required for DNA synthesis. MCM6 contributes to the DNA helicase activity of this complex and participates in the licensing of DNA replication origins during the G1 phase of the cell cycle.

In replication licensing, MCM2-7 is loaded onto chromatin by the ORC, Cdc6, and Cdt1 to form the pre-replicative complex. Activation of the licensed complex converts MCM2-7 into the active CMG helicase, which includes Cdc45 and the GINS complex, enabling bidirectional DNA unwinding and replication progression in S phase. As a core component of the replicative machinery, MCM6 works in concert with other MCM proteins to regulate the timing and efficiency of DNA replication and to maintain genome stability.

Genetic and regulatory aspects include a notable feature: the MCM6 gene contains regulatory elements that influence expression of the neighboring LCT gene, which encodes lactase. A well-studied polymorphism, rs4988235 (often described as the -13910*T variant), located in an intronic enhancer within MCM6, is associated with lactase persistence into adulthood in many populations by modulating LCT expression.

Expression and clinical relevance: MCM6 is expressed in most proliferating tissues and is conserved across eukaryotes. MCM proteins are commonly used as markers of cell proliferation in cancer diagnostics. Disruption of MCM6 function can contribute to replication stress and genomic instability, with altered expression observed in various cancers.