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

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 ? (Pol ?) plays a role in DNA replication under low deoxyribonucleotides condition triggered by hydroxyurea. In particular, the catalytic reaction performed by Pol ? is detrimental for RNase H deficient cells, causing DNA damage checkpoint activation and G2/M arrest. Moreover, a Pol ? 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 ? 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.
Mesh Terms:
Apoptosis, DNA Damage, DNA Repair, DNA Replication, DNA-Directed DNA Polymerase, Deoxyribonucleotides, G2 Phase Cell Cycle Checkpoints, Humans, Ribonuclease H, Saccharomyces cerevisiae
Nucleic Acids Res.
Date: Dec. 21, 2018
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