A Role for the Interactions between Polδ and PCNA Revealed by Analysis of pol3-01 Yeast Mutants

Shaked Nir Heyman, Mika Golan, Batia Liefshitz, Martin Kupiec

Research output: Contribution to journalArticlepeer-review

Abstract

Several DNA polymerases participate in DNA synthesis during genome replication and DNA repair. PCNA, a homotrimeric ring, acts as a processivity factor for DNA polymerases. PCNA also acts as a “landing pad” for proteins that interact with chromatin and DNA at the moving fork. The interaction between PCNA and polymerase delta (Polδ) is mediated by PIPs (PCNA-interacting peptides), in particular the one on Pol32, a regulatory subunit of Polδ. Here, we demonstrate that pol3-01, an exonuclease mutant of Polδ’s catalytic subunit, exhibits a weak interaction with Pol30 compared to the WT DNA polymerase. The weak interaction activates DNA bypass pathways, leading to increased mutagenesis and sister chromatid recombination. Strengthening pol3-01′s weak interaction with PCNA suppresses most of the phenotypes. Our results are consistent with a model in which Pol3-01 tends to detach from the chromatin, allowing an easier replacement of Polδ by the trans-lesion synthesis polymerase Zeta (Polz), thus leading to the increased mutagenic phenotype.

Original languageEnglish
Article number391
JournalGenes
Volume14
Issue number2
DOIs
StatePublished - Feb 2023

Keywords

  • DNA damage tolerance
  • DNA polymerase
  • PCNA
  • Saccharomyces cerevisiae
  • homologous recombination
  • mutagenesis

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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