caa a22 4500 569250587 20200516031152.0 cr unu---uuuuu 190725e20190521xx s 000 0 eng 10.3929/ethz-b-000353685 doi 10.1093/nar/gkz165 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/353685 RNase H activities counteract a toxic effect of Polymerase η in cells replicating with depleted dNTP pools [Elektronische Daten] [Alice Meroni, Giulia Maria Nava, Eliana Bianco, Lavinia Grasso, Elena Galati, Maria Cristina Bosio, Daria Delmastro, Marco Muzi-Falconi, Federico Lazzaro] Nucleic Acids Res. Open access ethresearch 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. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Meroni Alice joint author Nava Giulia Maria joint author Bianco Eliana joint author Grasso Lavinia joint author Galati Elena joint author Bosio Maria Cristina joint author Delmastro Daria joint author Muzi-Falconi Marco joint author Lazzaro Federico joint author Nucleic Acids Research Oxford : Oxford University Press 47 (9), pp. 4612-4623 1362-4962 http://hdl.handle.net/20.500.11850/353685 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/353685 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Meroni Alice joint author ETHRESEARCH 700 1- Nava Giulia Maria joint author ETHRESEARCH 700 1- Bianco Eliana joint author ETHRESEARCH 700 1- Grasso Lavinia joint author ETHRESEARCH 700 1- Galati Elena joint author ETHRESEARCH 700 1- Bosio Maria Cristina joint author ETHRESEARCH 700 1- Delmastro Daria joint author ETHRESEARCH 700 1- Muzi-Falconi Marco joint author ETHRESEARCH 700 1- Lazzaro Federico joint author ETHRESEARCH 773 0- Nucleic Acids Research Oxford : Oxford University Press 47 (9), pp. 4612-4623 1362-4962 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access