Eukaryotic Replication Fork

Abstract

In eukaryotic cells, DNA (deoxyribonucleic acid) synthesis occurs at specific sites that move through the genome called replication forks. Multiprotein complexes at these forks catalyse the synthesis of two new strands of DNA using parental strands as templates to produce two complete copies of the parental DNA. The eukaryotic replication fork machinery must deal with the chromatin and chromosome structure of eukaryotic genomes, be able to replicate DNA in the context of a complex cell cycle, and be able to deal with the constant threat of mutations that could arise due to replication of damaged DNA, all while trying to efficiently replicate the DNA with high fidelity. The resulting eukaryotic replication fork is a tightly controlled, yet incredibly efficient biological machine capable of synthesizing billions of base pairs of DNA in the span of hours.

Key Concepts:

  • Eukaryotic DNA replication requires the concerted action of multiple DNA polymerases and accessory factors that replicate the DNA with high efficiency and accuracy.

  • Eukaryotic chromosomes are replicated in a semidiscontinuous manner by replication forks that coordinate the simultaneous replication of the leading and lagging strands.

  • The eukaryotic replication machinery is equipped to displace histones that coat chromatin DNA and reconstitute fully functional nucleoprotein chromosomes after DNA replication.

Keywords: DNA replication; DNA polymerase; DNA synthesis; replication fork; checkpoint

Figure 1.

Schematic representation of a replication fork. Black lines – template DNA and red arrows – newly synthesized DNA. Positions of leading and lagging strands are indicated.

Figure 2.

Mechanism of Okazaki fragment synthesis and polymerase switching. Black lines – template DNA; red lines – newly synthesized DNA and green lines – RNA primers. A polymerase switch between DNA Pol α, RPA, RF‐C and DNA Pol δ, is shown in steps 1–4, starting with an RPA ‐coated ssDNA molecule that contains the 5′ end of a completed Okazaki fragment on the right. Even though proteins are shown freely diffusing, they probably remain transiently associated with the DNA as part of a replisome complex. Steps 5–7 indicate the flap displacement by Pol δ, and the RNA primer processing by Fen1 and DNA ligase 1.

Figure 3.

Model of a eukaryotic replication fork. Schematic representation of replication fork topology based on known protein–protein interactions and analogy to prokaryotic replication forks. Black lines – template DNA; red lines – newly synthesized DNA and green lines – RNA primers. Looping of the lagging strand template DNA allows the replication machinery to move in the direction of the leading strand while synthesizing the lagging strand in the opposite direction.

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How to Cite close
Walther, André P(Mar 2010) Eukaryotic Replication Fork. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001050.pub2]