Elserafy, M,, El-Shiekh, I,, Fleifel, D, et al. (5 more authors) (2021) A role for Rad5 in ribonucleoside monophosphate (rNMP) tolerance. Life Science Alliance, 4 (10). e202000966. ISSN 2575-1077
Abstract
Ribonucleoside monophosphate (rNMP) incorporation in genomic DNA poses a significant threat to genomic integrity. In addition to repair, DNA damage tolerance mechanisms ensure replication progression upon encountering unrepaired lesions. One player in the tolerance mechanism is Rad5, which is an E3 ubiquitin ligase and helicase. Here, we report a new role for yeast Rad5 in tolerating rNMP incorporation, in the absence of the bona fide ribonucleotide excision repair pathway via RNase H2. This role of Rad5 is further highlighted after replication stress induced by hydroxyurea or by increasing rNMP genomic burden using a mutant DNA polymerase (Pol ε - Pol2-M644G). We further demonstrate the importance of the ATPase and ubiquitin ligase domains of Rad5 in rNMP tolerance. These findings suggest a similar role for the human Rad5 homologues helicase-like transcription factor (HLTF) and SNF2 Histone Linker PHD RING Helicase (SHPRH) in rNMP tolerance, which may impact the response of cancer cells to replication stress-inducing therapeutics.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Elserafy et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 103844/Z/14/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 27 May 2022 11:19 |
Last Modified: | 11 Feb 2023 02:06 |
Status: | Published |
Publisher: | Life Science Alliance, LLC |
Refereed: | Yes |
Identification Number: | 10.26508/lsa.202000966 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:187389 |
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