Polymerase dynamics at the eukaryotic DNA replication fork.
This review discusses recent insights in the roles of DNA polymerases (Pol) delta and epsilon in eukaryotic DNA replication. A growing body of evidence specifies Pol epsilon as the leading strand DNA polymerase and Pol delta as the lagging strand polymerase during undisturbed DNA replication. New evidence supporting this model comes from the use of polymerase mutants that show an asymmetric mutator phenotype for certain mispairs, allowing an unambiguous strand assignment for these enzymes. On the lagging strand, Pol delta corrects errors made by Pol alpha during Okazaki fragment initiation. During Okazaki fragment maturation, the extent of strand displacement synthesis by Pol delta determines whether maturation proceeds by the short or long flap processing pathway. In the more common short flap pathway, Pol delta coordinates with the flap endonuclease FEN1 to degrade initiator RNA, whereas in the long flap pathway, RNA removal is initiated by the Dna2 nuclease/helicase.
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. burgers@biochem.wustl.edu
Peter M J
PM
Burgers
D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology*; D005057:Eukaryotic Cells / Q000166:cytology / Q000201:enzymology*; D045585:Flap Endonucleases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation
C022262:Okazaki fragments; D004247:DNA; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D004265:DNA Helicases; C509908:DNA2 protein, human