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Mechanism of Lagging-Strand DNA Replication in Eukaryotes

  • Joseph L. Stodola
  • Peter M. BurgersEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1042)

Abstract

This chapter focuses on the enzymes and mechanisms involved in lagging-strand DNA replication in eukaryotic cells. Recent structural and biochemical progress with DNA polymerase α-primase (Pol α) provides insights how each of the millions of Okazaki fragments in a mammalian cell is primed by the primase subunit and further extended by its polymerase subunit. Rapid kinetic studies of Okazaki fragment elongation by Pol δ illuminate events when the polymerase encounters the double-stranded RNA-DNA block of the preceding Okazaki fragment. This block acts as a progressive molecular break that provides both time and opportunity for the flap endonuclease 1 (FEN1) to access the nascent flap and cut it. The iterative action of Pol δ and FEN1 is coordinated by the replication clamp PCNA and produces a regulated degradation of the RNA primer, thereby preventing the formation of long-strand displacement flaps. Occasional long flaps are further processed by backup nucleases including Dna2.

Keywords

DNA replication Lagging strand Okazaki fragment maturation DNA polymerase α-primase DNA polymerase δ Flap endonuclease 1 Dna2 

Notes

Acknowledgments

The research in the authors’ laboratory is supported by grants from the US National Institutes of Health (GM032431, GM083970, and GM118129 to P.B). J.S. was supported in part by a grant from the USA-Israel Binational Science Foundation (2013358).

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© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiophysicsWashington University School of MedicineSaint LouisUSA

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