Liquid-liquid phase separation (LLPS) has been recently suggested as a new potential mechanism underpinning various organizational aspects of the cell, from the formation of sub-cellular, biomolecule enrichments to the assembly of organelles. In eukaryotes, DNA replication follows a strict temporal and spatial program that is majorly affected by the chromatin structure, the nuclear organization and the availability of limiting initiation factors, however the regulatory mechanisms driving the process have not been fully elucidated. Original data published lately revealed for the first time that the components of the pre-replicative complex, ORC, Cdc6 and Cdt1, are able to phase separate indicating a possible connection between LLPS and DNA replication. Here, we critically present these preliminary data and propose mechanistic models that could support this regulatory link and lead to new future research directions.
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