Regulation of S phase

Results Probl Cell Differ. 2006:42:31-63. doi: 10.1007/b137221.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cyclin-Dependent Kinases / physiology
  • DNA Replication / genetics
  • DNA Replication / physiology*
  • Gene Expression Regulation / physiology
  • Humans
  • Origin Recognition Complex
  • Replication Origin
  • S Phase*

Substances

  • Origin Recognition Complex
  • Cyclin-Dependent Kinases