Mechanism of lagging-strand DNA replication in eukaryotes

Joseph L. Stodola, Peter M. Burgers

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

29 Scopus citations


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.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Number of pages17
StatePublished - 2017

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


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


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