Nuclear localization of Schizosaccharomyces pombe Mcm2/Cdc19p requires MCMcomplex assembly

The:minichromosome maintenance (MCM) proteins MCM2-MCM7 are conserved eukar yotic replication factors that assemble in a heterohexameric complex. in fi ssion yeast, these proteins are nuclear throughout the cell cycle. In study ing the mechanism that regulates assembly of the MCM complex, we analyzed t he cis and trans elements required for nuclear localization of a single sub unit, Mcm2p. Mutation of any single mcm gene leads to redistribution of wil d-type MCM subunits to the cytoplasm, and this redistribution depends on an active nuclear export system. We identified the nuclear localization signa l sequences of Mcm2p and showed that these are required for nuclear targeti ng of other MCM subunits. Ln turn, Mcm2p must associate with other MCM prot eins for its proper localization; nuclear localization of MCM proteins thus requires assembly of MCM proteins in a complex. We suggest that coupling c omplex assembly to nuclear targeting and retention ensures that only intact heterohexameric:MCM complexes remain nuclear.