page_title: DNA re-replication
section_title: Two-state model for DNA replication regulation
hierarchical_section_title: DNA re-replication / Two-state model for DNA replication regulation
caption_attribution_description: English: Schematic depiction of the licensing of an S. cerevisiae replication origin in the prereplicative state.
context_page_description: DNA re-replication is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers. To prevent rereplication, eukaryotic cells have evolved multiple, overlapping mechanisms to inhibit chromosomal DNA from being partially or fully rereplicated in a given cell cycle. These control mechanisms rely on cyclin-dependent kinase activity. DNA replication control mechanisms cooperate to prevent the relicensing of replication origins and to activate cell cycle and DNA damage checkpoints. DNA rereplication must be strictly regulated to ensure that genomic information is faithfully transmitted through successive generations.
context_section_description: Early experimental evidence on the regulation of DNA replication suggests that replication origins exist in one of two states during the cell cycle: a prereplicative state in G1 and a postreplicative state from the moment of initiation until passage through mitosis.  Origins of replication alternate between these two distinct states during the cell cycle.  A licensing factor which is required for replication initiation binds to origins in the prereplicative state.  At the G1/S transition, the factor is inactivated and cannot be restored until the cell cycle has concluded.   The identification and characterization of the ORC, Cdc6, Cdt1, and the MCM complex proteins as the licensing factor gives credence to this model and suggests a means by which the oscillatory nature of CDKs in the cell cycle can regulate rereplication.
caption: S. cerevisiae origin in the prereplicative state. Assembly of the pre-replicative complex (pre-RC) readies the origin for firing.
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