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Evidence that DNA polymerase δ contributes to initiating leading strand DNA replication in Saccharomyces cerevisiae

Author

Listed:
  • Marta A. Garbacz

    (Research Triangle Park)

  • Scott A. Lujan

    (Research Triangle Park)

  • Adam B. Burkholder

    (Research Triangle Park)

  • Phillip B. Cox

    (Research Triangle Park)

  • Qiuqin Wu

    (Brandeis University)

  • Zhi-Xiong Zhou

    (Research Triangle Park)

  • James E. Haber

    (Brandeis University)

  • Thomas A. Kunkel

    (Research Triangle Park)

Abstract

To investigate nuclear DNA replication enzymology in vivo, we have studied Saccharomyces cerevisiae strains containing a pol2-16 mutation that inactivates the catalytic activities of DNA polymerase ε (Pol ε). Although pol2-16 mutants survive, they present very tiny spore colonies, increased doubling time, larger than normal cells, aberrant nuclei, and rapid acquisition of suppressor mutations. These phenotypes reveal a severe growth defect that is distinct from that of strains that lack only Pol ε proofreading (pol2-4), consistent with the idea that Pol ε is the major leading-strand polymerase used for unstressed DNA replication. Ribonucleotides are incorporated into the pol2-16 genome in patterns consistent with leading-strand replication by Pol δ when Pol ε is absent. More importantly, ribonucleotide distributions at replication origins suggest that in strains encoding all three replicases, Pol δ contributes to initiation of leading-strand replication. We describe two possible models.

Suggested Citation

  • Marta A. Garbacz & Scott A. Lujan & Adam B. Burkholder & Phillip B. Cox & Qiuqin Wu & Zhi-Xiong Zhou & James E. Haber & Thomas A. Kunkel, 2018. "Evidence that DNA polymerase δ contributes to initiating leading strand DNA replication in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03270-4
    DOI: 10.1038/s41467-018-03270-4
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    Cited by:

    1. Zuanning Yuan & Roxana Georgescu & Huilin Li & Michael E. O’Donnell, 2023. "Molecular choreography of primer synthesis by the eukaryotic Pol α-primase," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Sameera Vipat & Dipika Gupta & Sagun Jonchhe & Hele Anderspuk & Eli Rothenberg & Tatiana N. Moiseeva, 2022. "The non-catalytic role of DNA polymerase epsilon in replication initiation in human cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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