MCMBP maintains genome integrity by protecting the MCM subunits from degradation

The hetero-hexameric MCM2-7 helicase plays a central role in eukaryotic DNA replication. The expression of MCM2-7 is maintained at a high level for creating dormant origins, which are important for maintaining genome integrity. However, other than transcriptional activation for the de novo synthesis, little is known about how cells maintain a high level of MCM2-7. We show that human MCMBP is a short-lived nuclear protein associating mainly with MCM5, 6, and 7. Loss of MCMBP down-regulates MCM2-7, leading to replication stress and DNA-damage accumulation. Our work demonstrates MCMBP protects the MCM subunits from degradation and suggests its chaperone-like role to achieve a high level of functional MCM2-7 using the nascent and recycled subunits.