How Dormant Origins Promote Complete Genome Replication

Trends Biochem Sci. 2011 Aug;36(8):405-14. doi: 10.1016/j.tibs.2011.05.002. Epub 2011 Jun 7.

Abstract

Many replication origins that are licensed by loading MCM2-7 complexes in G1 are not normally used. Activation of these dormant origins during S phase provides a first line of defence for the genome if replication is inhibited. When replication forks fail, dormant origins are activated within regions of the genome currently engaged in replication. At the same time, DNA damage-response kinases activated by the stalled forks preferentially suppress the assembly of new replication factories, thereby ensuring that chromosomal regions experiencing replicative stress complete synthesis before new regions of the genome are replicated. Mice expressing reduced levels of MCM2-7 have fewer dormant origins, are cancer-prone and are genetically unstable, demonstrating the importance of dormant origins for preserving genome integrity. We review the function of dormant origins, the molecular mechanism of their regulation and their physiological implications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / genetics*
  • DNA Replication / genetics*
  • DNA-Binding Proteins / genetics
  • Genes, Tumor Suppressor
  • Mice
  • Minichromosome Maintenance Complex Component 2
  • Minichromosome Maintenance Complex Component 3
  • Minichromosome Maintenance Complex Component 4
  • Minichromosome Maintenance Complex Component 6
  • Minichromosome Maintenance Complex Component 7
  • Nuclear Proteins / genetics*
  • Replication Origin / genetics*
  • S Phase / genetics
  • Silencer Elements, Transcriptional / genetics*
  • Stochastic Processes

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MCM5 protein, human
  • Mcm3 protein, mouse
  • Nuclear Proteins
  • MCM2 protein, human
  • MCM4 protein, human
  • MCM6 protein, human
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 2
  • Minichromosome Maintenance Complex Component 3
  • Minichromosome Maintenance Complex Component 4
  • Minichromosome Maintenance Complex Component 6
  • Minichromosome Maintenance Complex Component 7