Coupling mitosis to DNA replication: The emerging role of the histone H4-lysine 20 methyltransferase PR-Set7

To ensure accurate inheritance of genetic information through cell proliferation, chromosomes must be precisely copied only during S phase, and then correctly condensed and segregated during mitosis. Several new findings suggest that this tight coupling between DNA replication and mitosis is in part controlled by cell cycle regulated chromatin modifications, in particular due to the changing activity of lysine methyltransferase PR-Set7/SET8 that is responsible for the monomethylation of histone H4 at lysine 20. Cell cycle oscillation of PR-Set7 is orchestrated by ubiquitin-mediated proteolysis, and interference with this regulatory process leads to unscheduled licensing of replication origins and altered timing of mitotic chromosome compaction. This review provides an overview of how PR-Set7 regulates these two cell cycle events and highlights questions that remain to be addressed.