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RNase H activities counteract a toxic effect of Polymerase η in cells replicating with depleted dNTP pools.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2019 May 21; Vol. 47 (9), pp. 4612-4623. - Publication Year :
- 2019
-
Abstract
- 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.<br /> (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 47
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 30847483
- Full Text :
- https://doi.org/10.1093/nar/gkz165