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|
MERONI, ALICE (Primo)
NAVA, GIULIA MARIA (Secondo)
MUZI FALCONI, MARCO (Penultimo) (Corresponding)
LAZZARO, FEDERICO (Ultimo) (Corresponding)
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
Settore BIO/18 - Genetica
|Data di pubblicazione:||21-mag-2019|
|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|