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

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.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages117-133
Number of pages17
DOIs
StatePublished - 2017

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1042
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

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

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