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.
RNase H activities counteract a toxic effect of Polymerase in cells replicating with depleted dNTP pools / A. Meroni, G.M. Nava, E. Bianco, L. Grasso, E. Galati, M.C. Bosio, D. Dalmastro, M. Muzi Falconi, F. Lazzaro. - In: NUCLEIC ACIDS RESEARCH. - ISSN 1362-4962. - 7:9(2019 May 21), pp. 4612-4623.
Titolo: | RNase H activities counteract a toxic effect of Polymerase in cells replicating with depleted dNTP pools |
Autori: | MERONI, ALICE (Primo) NAVA, GIULIA MARIA (Secondo) LAZZARO, FEDERICO (Ultimo) (Corresponding) |
Settore Scientifico Disciplinare: | Settore BIO/11 - Biologia Molecolare Settore BIO/18 - Genetica |
Data di pubblicazione: | 21-mag-2019 |
Rivista: | |
Tipologia: | Article (author) |
Data ahead of print / Data di stampa: | feb-2019 |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1093/nar/gkz165 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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