The Initiation of Eukaryotic DNA Replication

Annu Rev Biochem. 2022 Jun 21:91:107-131. doi: 10.1146/annurev-biochem-072321-110228. Epub 2022 Mar 23.


DNA replication in eukaryotic cells initiates from large numbers of sites called replication origins. Initiation of replication from these origins must be tightly controlled to ensure the entire genome is precisely duplicated in each cell cycle. This is accomplished through the regulation of the first two steps in replication: loading and activation of the replicative DNA helicase. Here we describe what is known about the mechanism and regulation of these two reactions from a genetic, biochemical, and structural perspective, focusing on recent progress using proteins from budding yeast.

Keywords: DNA replication; cell cycle; cryo–electron microscopy.

Publication types

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

MeSH terms

  • Cell Cycle / genetics
  • DNA Replication
  • Eukaryota* / genetics
  • Eukaryotic Cells* / metabolism
  • Replication Origin