Cyclin-dependent kinase-dependent initiation of chromosomal DNA replication

Curr Opin Cell Biol. 2010 Dec;22(6):766-71. doi: 10.1016/j.ceb.2010.07.015. Epub 2010 Aug 20.

Abstract

Cyclin-dependent kinase (CDK) is essential for the initiation of chromosomal DNA replication. CDK phosphorylates two yeast replication proteins, Sld2 and Sld3, both of which bind to another replication protein, Dpb11 when phosphorylated. These interactions are essential and are the minimal requirements for CDK activation of chromosomal DNA replication. This review discusses how these phosphorylation-dependent interactions initiate DNA replication through the formation of the pre-loading complex (pre-LC) and its interaction with phosphorylated Sld3 on replication origins. These steps are further regulated by multisite phosphorylation of Sld2. Sld3, on the other hand, must be turned over to reassociate with origins. Pol ɛ functions as a component of the pre-LC as well as a replicative DNA polymerase at replication forks.

Publication types

  • Review

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromosomes, Fungal / genetics*
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • DNA Polymerase II / metabolism
  • DNA Replication*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Phosphorylation
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • SLD2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sld3 protein, S cerevisiae
  • Cyclin-Dependent Kinases
  • DNA Polymerase II