Quality control in the initiation of eukaryotic DNA replication

Philos Trans R Soc Lond B Biol Sci. 2011 Dec 27;366(1584):3545-53. doi: 10.1098/rstb.2011.0073.


Origins of DNA replication must be regulated to ensure that the entire genome is replicated precisely once in each cell cycle. In human cells, this requires that tens of thousands of replication origins are activated exactly once per cell cycle. Failure to do so can lead to cell death or genome rearrangements such as those associated with cancer. Systems ensuring efficient initiation of replication, while also providing a robust block to re-initiation, play a crucial role in genome stability. In this review, I will discuss some of the strategies used by cells to ensure once per cell cycle replication and provide a quantitative framework to evaluate the relative importance and efficiency of individual pathways involved in this regulation.

Publication types

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

MeSH terms

  • Animals
  • Bacteria / genetics
  • Bacteria / metabolism
  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Replication*
  • Eukaryota / genetics*
  • Eukaryota / metabolism
  • Humans
  • Origin Recognition Complex / genetics
  • Origin Recognition Complex / metabolism
  • Replication Origin


  • Cell Cycle Proteins
  • Origin Recognition Complex