- In recent years considerable effort has been invested toward understanding the molecular mechanisms that regulate and restrict DNA replication to once per each cell cycle. An important contribution came from studying the phenomenon of endoreduplication-an endonuclear duplication of chromosomes which occurs in the absence of mitosis leading to the production of chromosomes with doubling series of chromatids. Because endoreduplicating nuclei retain the capability of replication without passing through mitosis, they provide a unique system for studying the molecular mechanisms that restrict DNA replication to once per cycle. Three types of endoreduplication can be identified: I, multiple initiations within a given S phase; II, reoccurring S phase; and III, repeated S and Gap phases. Each of these illuminates a different control level acting over the onset of S phase, which coordinately restrict DNA synthesis to once per each cell cycle.