Chapter title |
Mechanism of Lagging-Strand DNA Replication in Eukaryotes
|
---|---|
Chapter number | 6 |
Book title |
DNA Replication
|
Published in |
Advances in experimental medicine and biology, January 2017
|
DOI | 10.1007/978-981-10-6955-0_6 |
Pubmed ID | |
Book ISBNs |
978-9-81-106954-3, 978-9-81-106955-0
|
Authors |
Joseph L. Stodola, Peter M. Burgers, Stodola, Joseph L., Burgers, Peter M. |
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. |
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