• Reference Type: Journal Article | Research Support, Non-U.S. Gov't
  Moreno SP, et al. (2014) Polyubiquitylation drives replisome disassembly at the termination of DNA replication. Science 346(6208):477-81 PMID: 25342805
  • SGD Paper
  • DOI full text
  • PubMed

  Resolution of replication forks during termination of DNA replication is essential for accurate duplication of eukaryotic genomes. Here we present evidence consistent with the idea that polyubiquitylation of a replisome component (Mcm7) leads to its disassembly at the converging terminating forks because of the action of the p97/VCP/Cdc48 protein remodeler. Using Xenopus laevis egg extract, we have shown that blocking polyubiquitylation results in the prolonged association of the active helicase with replicating chromatin. The Mcm7 subunit is the only component of the active helicase that we find polyubiquitylated during replication termination. The observed polyubiquitylation is followed by disassembly of the active helicase dependent on p97/VCP/Cdc48. Altogether, our data provide insight into the mechanism of replisome disassembly during eukaryotic DNA replication termination.

• Reference Type: Journal Article | Research Support, Non-U.S. Gov't
  Maric M, et al. (2014) Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication. Science 346(6208):1253596 PMID: 25342810
  • SGD Paper
  • DOI full text
  • PMC full text
  • PubMed

  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.

• Reference Type: Journal Article | Research Support, Non-U.S. Gov't
  Moreno SP, et al. (2014) Polyubiquitylation drives replisome disassembly at the termination of DNA replication. Science 346(6208):477-81 PMID: 25342805
  • SGD Paper
  • DOI full text
  • PubMed

  Resolution of replication forks during termination of DNA replication is essential for accurate duplication of eukaryotic genomes. Here we present evidence consistent with the idea that polyubiquitylation of a replisome component (Mcm7) leads to its disassembly at the converging terminating forks because of the action of the p97/VCP/Cdc48 protein remodeler. Using Xenopus laevis egg extract, we have shown that blocking polyubiquitylation results in the prolonged association of the active helicase with replicating chromatin. The Mcm7 subunit is the only component of the active helicase that we find polyubiquitylated during replication termination. The observed polyubiquitylation is followed by disassembly of the active helicase dependent on p97/VCP/Cdc48. Altogether, our data provide insight into the mechanism of replisome disassembly during eukaryotic DNA replication termination.

• Reference Type: Journal Article | Research Support, Non-U.S. Gov't
  Maric M, et al. (2014) Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication. Science 346(6208):1253596 PMID: 25342810
  • SGD Paper
  • DOI full text
  • PMC full text
  • PubMed

  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.

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