The contribution of dormant origins to genome stability: from cell biology to human genetics

DNA Repair (Amst). 2014 Jul;19(100):182-9. doi: 10.1016/j.dnarep.2014.03.012. Epub 2014 Apr 24.


The ability of a eukaryotic cell to precisely and accurately replicate its DNA is crucial to maintain genome stability. Here we describe our current understanding of the process by which origins are licensed for DNA replication and review recent work suggesting that fork stalling has exerted a strong selective pressure on the positioning of licensed origins. In light of this, we discuss the complex and disparate phenotypes observed in mouse models and humans patients that arise due to defects in replication licensing proteins.

Keywords: Dormant origins; MCM2–7; Meier–Gorlin; Origin licensing; Pre-RC; Replication origins.

Publication types

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

MeSH terms

  • Animals
  • DNA Replication / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genetics, Medical*
  • Genomic Instability / genetics*
  • Humans
  • Mice
  • Minichromosome Maintenance Proteins / genetics
  • Mitosis / genetics
  • Replication Origin / genetics*


  • DNA-Binding Proteins
  • Minichromosome Maintenance Proteins