title: New Insights into the Mechanism of DNA Duplication by the Eukaryotic Replisome.
abstract: The DNA replication machinery, or replisome, is a macromolecular complex that combines DNA unwinding, priming and synthesis activities. In eukaryotic cells, the helicase and polymerases are multi-subunit, highly-dynamic assemblies whose structural characterization requires an integrated approach. Recent studies have combined single-particle electron cryo-microscopy and protein crystallography to gain insights into the mechanism of DNA duplication by the eukaryotic replisome. We review current understanding of how replication fork unwinding by the CMG helicase is coupled to leading-strand synthesis by polymerase (Pol) ɛ and lagging-strand priming by Pol α/primase, and discuss emerging principles of replisome organization.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK. Electronic address: lp212@cam.ac.uk.
authors.forename: Luca
authors.initials: L
authors.lastname: Pellegrini
authors.affiliation: Macromolecular Machines Laboratory, Clare Hall Laboratory, The Francis Crick Institute, Blanche Lane, South Mimms EN6 3LD, UK. Electronic address: alessandro.costa@crick.ac.uk.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Costa
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004256:DNA Polymerase I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004257:DNA Polymerase II / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019915:DNA Primase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D015870:Gene Expression; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D062105:Molecular Docking Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: C113571:CDC45 protein, human; D018797:Cell Cycle Proteins; D004247:DNA; D019915:DNA Primase; C116932:DNA polymerase alpha-primase; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D064110:Minichromosome Maintenance Proteins