Notch and minichromosome maintenance (MCM) proteins: integration of two ancestral pathways in cell cycle control.

Notch transmembrane receptors govern a highly evolutionarily conserved intercellular signaling mechanism activated by the engagement of Notch receptors by their cognate ligands expressed on neighboring cells. The subsequently cleaved intracellular domain of Notch receptors translocates to the nucleus where it interacts with the transcriptional regulator CSL, thereby regulating expression of target genes. The Notch pathway controls cell fate by regulating proliferation, differentiation, and apoptosis. Mini-chromosome maintenance (MCM) proteins are components of the prereplicative complex (pre-RC) that are essential for DNA replication. It has recently been shown that activated Notch downregulates mini-chromosome-maintenance (MCM) proteins MCM2 and MCM6 by a CSL-dependent mechanism. Here, we review the canonical pathway mediated by Notch receptors and discuss recent findings connecting the Notch pathway with the ancestral MCM complex during cell cycle progression.