Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication

Science. 2014 Oct 24;346(6208):1253596. doi: 10.1126/science.1253596.

Abstract

Chromosome replication is initiated by a universal mechanism in eukaryotic cells, involving the assembly and activation at replication origins of the CMG (Cdc45-MCM-GINS) DNA helicase, which is essential for the progression of replication forks. Disassembly of CMG is likely to be a key regulated step at the end of chromosome replication, but the mechanism was unknown until now. Here we show that the ubiquitin ligase known as SCF(Dia2) promotes ubiquitylation of CMG during the final stages of chromosome replication in Saccharomyces cerevisiae. The Cdc48/p97 segregase then associates with ubiquitylated CMG, leading rapidly to helicase disassembly. These findings indicate that the end of chromosome replication in eukaryotes is controlled in a similarly complex fashion to the much-better-characterized initiation step.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Cell Cycle Proteins / metabolism*
  • DNA Replication*
  • DNA-Binding Proteins / metabolism*
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism*
  • Minichromosome Maintenance Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Ribonucleoprotein, U4-U6 Small Nuclear / metabolism*
  • Ribonucleoprotein, U5 Small Nuclear / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Valosin Containing Protein

Substances

  • CDC45 protein, S cerevisiae
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Dia2 protein, S cerevisiae
  • F-Box Proteins
  • Nuclear Proteins
  • PRP8 protein, S cerevisiae
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • Ribonucleoprotein, U5 Small Nuclear
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligases
  • Adenosine Triphosphatases
  • CDC48 protein, S cerevisiae
  • Minichromosome Maintenance Proteins
  • Valosin Containing Protein