title: Polyubiquitylation drives replisome disassembly at the termination of DNA replication.
abstract: 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.
authors.affiliation: School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.
authors.forename: Sara Priego
authors.initials: SP
authors.lastname: Moreno
authors.affiliation: School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.
authors.forename: Rachael
authors.initials: R
authors.lastname: Bailey
authors.affiliation: School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Campion
authors.affiliation: School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Herron
authors.affiliation: School of Cancer Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK. a.gambus@bham.ac.uk.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gambus
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D004261:DNA Replication; D064168:Minichromosome Maintenance Complex Component 7 / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000074405:Valosin Containing Protein; D014982:Xenopus laevis
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D025801:Ubiquitin; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D064168:Minichromosome Maintenance Complex Component 7; D000074405:Valosin Containing Protein