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Annu Rev Biochem. 2017 Jun 20;86:417-438. doi: 10.1146/annurev-biochem-061516-044709. Epub 2017 Mar 1.

Eukaryotic DNA Replication Fork.

Author information

1
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110; email: burgers@biochem.wustl.edu.
2
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.

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.

KEYWORDS:

CMG helicase; DNA polymerase; DNA primase; Okazaki fragment; replisome coordination

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