prereplicative

Prereplicative is an adjective used in biology to describe processes or states that occur before the initiation of DNA replication. In eukaryotic cells, prereplicative concepts are most closely tied to origin licensing, the step that equips replication origins to fire during S phase.

Origin licensing involves the assembly of the prereplicative complex (pre-RC) at replication origins during G1. The Origin Recognition Complex (ORC) binds origins and recruits the proteins Cdc6 and Cdt1, which together load the MCM2-7 helicase complex onto DNA. The resulting pre-RC marks origins as competent for replication but keeps them inactive until appropriate S-phase signals trigger activation.

Activation occurs in S phase when S-phase cyclin-dependent kinases (CDKs) and other kinases promote the formation of a pre-initiation complex and helicase activation, leading to origin firing and DNA synthesis. The prereplicative state thus serves as a licensing mechanism that ensures replication starts only once per origin per cell cycle.

Regulation of prereplicative licensing is essential for genomic stability. Inhibitors such as geminin and controlled degradation of licensing factors prevent re-licensing after initiation, helping to avert re-replication and DNA damage.

The concept is widely described in studies of yeast, plants, and animal systems, reflecting a conserved strategy to coordinate DNA replication with cell-cycle progression. Prereplicative processes underline how cells prepare replication origins in advance and control their activation to maintain genome integrity.