Regulation of S phase.
Regulation of DNA replication is critical for accurate and timely dissemination of genomic material to daughter cells. The cell uses a variety of mechanisms to control this aspect of the cell cycle. There are various determinants of origin identification, as well as a large number of proteins required to load replication complexes at these defined genomic regions. A pre-Replication Complex (pre-RC) associates with origins in the G1 phase. This complex includes the Origin Recognition Complex (ORC), which serves to recognize origins, the putative helicase MCM2-7, and other factors important for complex assembly. Following pre-RC loading, a pre-Initiation Complex (pre-IC) builds upon the helicase with factors required for eventual loading of replicative polymerases. The chromatin association of these two complexes is temporally distinct, with pre-RC being inhibited, and pre-IC being activated by cyclin-dependent kinases (Cdks). This regulation is the basis for replication licensing, which allows replication to occur at a specific time once, and only once, per cell cycle. By preventing extra rounds of replication within a cell cycle, or by ensuring the cell cycle cannot progress until the environmental and intracellular conditions are most optimal, cells are able to carry out a successful replication cycle with minimal mutations.
Teer
Jamie K
JK
Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115, USA.
Dutta
Anindya
A
D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D004261:DNA Replication / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051738:Origin Recognition Complex; D018741:Replication Origin; D016196:S Phase
D051738:Origin Recognition Complex; D018844:Cyclin-Dependent Kinases