title: Eukaryotic DNA Replication Fork.
abstract: This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110; email: burgers@biochem.wustl.edu.
authors.forename: Peter M J
authors.initials: PMJ
authors.lastname: Burgers
authors.affiliation: Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; email: kunkel@niehs.nih.gov.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004256:DNA Polymerase I / Q000235:genetics / Q000378:metabolism; D004257:DNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C113571:CDC45 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C547590:GINS1 protein, human; C022262:Okazaki fragments; D004247:DNA; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D004265:DNA Helicases; D064110:Minichromosome Maintenance Proteins
keywords: CMG helicase; DNA polymerase; DNA primase; Okazaki fragment; replisome coordination