Polymerase dynamics at the eukaryotic DNA replication fork - PubMed (original) (raw)

Review

Polymerase dynamics at the eukaryotic DNA replication fork

Peter M J Burgers. J Biol Chem. 2009.

Abstract

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.

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Figures

FIGURE 1.

FIGURE 1.

Replication fork models. Left, model showing the primary replication functions of Pol δ and Pol ε; right, hypothetical replication fork formed by remodeling of the normal fork following replication stress or at specific chromosomal regions.

FIGURE 2.

FIGURE 2.

Coordination between Pol δ and FEN1 in Okazaki fragment maturation. During Okazaki fragment maturation, Pol δ and FEN1 go through multiple cycles of displacement synthesis, molecular handoffs, and cutting (nick translation) until all initiator RNA (iRNA) has been degraded. During FEN1 dysfunction, idling maintains Pol δ at the nick position. Exo, exonuclease.

FIGURE 3.

FIGURE 3.

Distribution between short and long flap removal pathways. The main pathway (thick arrows) involves limited strand displacement by Pol δ, followed by FEN1 cutting of the single nucleotide flap. This process is iterated until all initiator RNA (iRNA; red) is degraded (Nick Translation). Long flap formation (dashed arrows) results from excessive strand displacement synthesis. It is reduced by the exonuclease (Exo) activity of Pol δ (Idling) and promoted by the actions of Pol32 or Pif1. Dna2 cuts long flaps that are further degraded to precise nicks by FEN1 or the exonuclease activity of Pol δ (Long Flap Processing).

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