RNase H activities counteract a toxic effect of Polymerase in cells replicating with depleted dNTP pools
Articolo
Data di Pubblicazione:
2019
Citazione:
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.
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 (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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
A. Meroni, G.M. Nava, E. Bianco, L. Grasso, E. Galati, M.C. Bosio, D. Dalmastro, M. Muzi Falconi, F. Lazzaro
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