RNase H activities counteract a toxic effect of Polymerase η in cells replicating with depleted dNTP pools

Nucleic Acids Res. 2019 May 21;47(9):4612-4623. doi: 10.1093/nar/gkz165.


RNA:DNA hybrids are transient physiological intermediates that arise during several cellular processes such as DNA replication. In pathological situations, they may stably accumulate and pose a threat to genome integrity. Cellular RNase H activities process these structures to restore the correct DNA:DNA sequence. Yeast cells lacking RNase H are negatively affected by depletion of deoxyribonucleotide pools necessary for DNA replication. Here we show that the translesion synthesis DNA polymerase η (Pol η) plays a role in DNA replication under low deoxyribonucleotides condition triggered by hydroxyurea. In particular, the catalytic reaction performed by Pol η is detrimental for RNase H deficient cells, causing DNA damage checkpoint activation and G2/M arrest. Moreover, a Pol η mutant allele with enhanced ribonucleotide incorporation further exacerbates the sensitivity to hydroxyurea of cells lacking RNase H activities. Our data are compatible with a model in which Pol η activity facilitates the formation or stabilization of RNA:DNA hybrids at stalled replication forks. However, in a scenario where RNase H activity fails to restore DNA, these hybrids become highly toxic for cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • DNA Damage / genetics
  • DNA Repair / genetics
  • DNA Replication / genetics*
  • DNA-Directed DNA Polymerase / genetics*
  • Deoxyribonucleotides / genetics
  • G2 Phase Cell Cycle Checkpoints / genetics
  • Humans
  • Ribonuclease H / genetics*
  • Saccharomyces cerevisiae / genetics*


  • Deoxyribonucleotides
  • DNA-Directed DNA Polymerase
  • Rad30 protein
  • Ribonuclease H