Pif1 Removes a Rap1-dependent Barrier to the Strand Displacement Activity of DNA Polymerase δ

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2016 Mar 23

PMID 27001517

Citations 26

Authors

Katrina N Koc

Saurabh P Singh

Joseph L Stodola

Peter M Burgers

Roberto Galletto

Affiliations

Soon will be listed here.

Abstract

Using an in vitro reconstituted system in this work we provide direct evidence that the yeast repressor/activator protein 1 (Rap1), tightly bound to its consensus site, forms a strong non-polar barrier for the strand displacement activity of DNA polymerase δ. We propose that relief of inhibition may be mediated by the activity of an accessory helicase. To this end, we show that Pif1, a 5'-3' helicase, not only stimulates the strand displacement activity of Pol δ but it also allows efficient replication through the block, by removing bound Rap1 in front of the polymerase. This stimulatory activity of Pif1 is not limited to the displacement of a single Rap1 molecule; Pif1 also allows Pol δ to carry out DNA synthesis across an array of bound Rap1 molecules that mimics a telomeric DNA-protein assembly. This activity of Pif1 represents a novel function of this helicase during DNA replication.

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References

Gomes X, Gary S, Burgers P . Overproduction in Escherichia coli and characterization of yeast replication factor C lacking the ligase homology domain. J Biol Chem. 2000; 275(19):14541-9. DOI: 10.1074/jbc.275.19.14541. View

Taylor H, OReilly M, Leslie A, Rhodes D . How the multifunctional yeast Rap1p discriminates between DNA target sites: a crystallographic analysis. J Mol Biol. 2000; 303(5):693-707. DOI: 10.1006/jmbi.2000.4161. View

Bae S, Bae K, Kim J, Seo Y . RPA governs endonuclease switching during processing of Okazaki fragments in eukaryotes. Nature. 2001; 412(6845):456-61. DOI: 10.1038/35086609. View

Grossi S, Bianchi A, Damay P, Shore D . Telomere formation by rap1p binding site arrays reveals end-specific length regulation requirements and active telomeric recombination. Mol Cell Biol. 2001; 21(23):8117-28. PMC: 99977. DOI: 10.1128/MCB.21.23.8117-8128.2001. View

Maga G, Villani G, Tillement V, Stucki M, Locatelli G, Frouin I . Okazaki fragment processing: modulation of the strand displacement activity of DNA polymerase delta by the concerted action of replication protein A, proliferating cell nuclear antigen, and flap endonuclease-1. Proc Natl Acad Sci U S A. 2001; 98(25):14298-303. PMC: 64676. DOI: 10.1073/pnas.251193198. View

Ivessa A, Zhou J, Schulz V, Monson E, Zakian V . Saccharomyces Rrm3p, a 5' to 3' DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA. Genes Dev. 2002; 16(11):1383-96. PMC: 186315. DOI: 10.1101/gad.982902. View

Jin Y, Ayyagari R, Resnick M, Gordenin D, Burgers P . Okazaki fragment maturation in yeast. II. Cooperation between the polymerase and 3'-5'-exonuclease activities of Pol delta in the creation of a ligatable nick. J Biol Chem. 2002; 278(3):1626-33. DOI: 10.1074/jbc.M209803200. View

Ayyagari R, Gomes X, Gordenin D, Burgers P . Okazaki fragment maturation in yeast. I. Distribution of functions between FEN1 AND DNA2. J Biol Chem. 2002; 278(3):1618-25. DOI: 10.1074/jbc.M209801200. View

Kobayashi T . The replication fork barrier site forms a unique structure with Fob1p and inhibits the replication fork. Mol Cell Biol. 2003; 23(24):9178-88. PMC: 309713. DOI: 10.1128/MCB.23.24.9178-9188.2003. View

10.

Ivessa A, Lenzmeier B, Bessler J, Goudsouzian L, Schnakenberg S, Zakian V . The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past nonhistone protein-DNA complexes. Mol Cell. 2003; 12(6):1525-36. DOI: 10.1016/s1097-2765(03)00456-8. View

11.

Makovets S, Herskowitz I, Blackburn E . Anatomy and dynamics of DNA replication fork movement in yeast telomeric regions. Mol Cell Biol. 2004; 24(9):4019-31. PMC: 387773. DOI: 10.1128/MCB.24.9.4019-4031.2004. View

12.

Brewer B, FANGMAN W . A replication fork barrier at the 3' end of yeast ribosomal RNA genes. Cell. 1988; 55(4):637-43. DOI: 10.1016/0092-8674(88)90222-x. View

13.

Linskens M, Huberman J . Organization of replication of ribosomal DNA in Saccharomyces cerevisiae. Mol Cell Biol. 1988; 8(11):4927-35. PMC: 365586. DOI: 10.1128/mcb.8.11.4927-4935.1988. View

14.

Henricksen L, Umbricht C, Wold M . Recombinant replication protein A: expression, complex formation, and functional characterization. J Biol Chem. 1994; 269(15):11121-32. View

15.

Konig P, Giraldo R, CHAPMAN L, Rhodes D . The crystal structure of the DNA-binding domain of yeast RAP1 in complex with telomeric DNA. Cell. 1996; 85(1):125-36. DOI: 10.1016/s0092-8674(00)81088-0. View

16.

Tishkoff D, Filosi N, Gaida G, Kolodner R . A novel mutation avoidance mechanism dependent on S. cerevisiae RAD27 is distinct from DNA mismatch repair. Cell. 1997; 88(2):253-63. DOI: 10.1016/s0092-8674(00)81846-2. View

17.

Kobayashi T, Horiuchi T . A yeast gene product, Fob1 protein, required for both replication fork blocking and recombinational hotspot activities. Genes Cells. 1996; 1(5):465-74. DOI: 10.1046/j.1365-2443.1996.d01-256.x. View

18.

Burgers P, Gerik K . Structure and processivity of two forms of Saccharomyces cerevisiae DNA polymerase delta. J Biol Chem. 1998; 273(31):19756-62. DOI: 10.1074/jbc.273.31.19756. View

19.

Garg P, Stith C, Sabouri N, Johansson E, Burgers P . Idling by DNA polymerase delta maintains a ligatable nick during lagging-strand DNA replication. Genes Dev. 2004; 18(22):2764-73. PMC: 528896. DOI: 10.1101/gad.1252304. View

20.

Fortune J, Stith C, Kissling G, Burgers P, Kunkel T . RPA and PCNA suppress formation of large deletion errors by yeast DNA polymerase delta. Nucleic Acids Res. 2006; 34(16):4335-41. PMC: 1636344. DOI: 10.1093/nar/gkl403. View