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.