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PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage

PrimPol is a recently identified member of the archaeo-eukaryote primase (AEP) family of primase-polymerases. It has been shown that this mitochondrial and nuclear localized enzyme plays roles in the maintenance of both unperturbed replication fork progression and in the bypass of lesions after DNA...

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Autores principales: Bailey, Laura J., Bianchi, Julie, Hégarat, Nadia, Hochegger, Helfrid, Doherty, Aidan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889237/
https://www.ncbi.nlm.nih.gov/pubmed/26694751
http://dx.doi.org/10.1080/15384101.2015.1128597
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author Bailey, Laura J.
Bianchi, Julie
Hégarat, Nadia
Hochegger, Helfrid
Doherty, Aidan J.
author_facet Bailey, Laura J.
Bianchi, Julie
Hégarat, Nadia
Hochegger, Helfrid
Doherty, Aidan J.
author_sort Bailey, Laura J.
collection PubMed
description PrimPol is a recently identified member of the archaeo-eukaryote primase (AEP) family of primase-polymerases. It has been shown that this mitochondrial and nuclear localized enzyme plays roles in the maintenance of both unperturbed replication fork progression and in the bypass of lesions after DNA damage. Here, we utilized an avian (DT40) knockout cell line to further study the consequences of loss of PrimPol (PrimPol(−/−)) on the downstream maintenance of cells after UV damage. We report that PrimPol(−/−) cells are more sensitive to UV-C irradiation in colony survival assays than Pol η-deficient cells. Although this increased UV sensitivity is not evident in cell viability assays, we show that this discrepancy is due to an enhanced checkpoint arrest after UV-C damage in the absence of PrimPol. PrimPol(−/−) arrested cells become stalled in G2, where they are protected from UV-induced cell death. Despite lacking an enzyme required for the bypass and maintenance of replication fork progression in the presence of UV damage, we show that PrimPol(−/−) cells actually have an advantage in the presence of a Chk1 inhibitor due to their slow progression through S-phase.
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spelling pubmed-48892372016-06-15 PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage Bailey, Laura J. Bianchi, Julie Hégarat, Nadia Hochegger, Helfrid Doherty, Aidan J. Cell Cycle Report PrimPol is a recently identified member of the archaeo-eukaryote primase (AEP) family of primase-polymerases. It has been shown that this mitochondrial and nuclear localized enzyme plays roles in the maintenance of both unperturbed replication fork progression and in the bypass of lesions after DNA damage. Here, we utilized an avian (DT40) knockout cell line to further study the consequences of loss of PrimPol (PrimPol(−/−)) on the downstream maintenance of cells after UV damage. We report that PrimPol(−/−) cells are more sensitive to UV-C irradiation in colony survival assays than Pol η-deficient cells. Although this increased UV sensitivity is not evident in cell viability assays, we show that this discrepancy is due to an enhanced checkpoint arrest after UV-C damage in the absence of PrimPol. PrimPol(−/−) arrested cells become stalled in G2, where they are protected from UV-induced cell death. Despite lacking an enzyme required for the bypass and maintenance of replication fork progression in the presence of UV damage, we show that PrimPol(−/−) cells actually have an advantage in the presence of a Chk1 inhibitor due to their slow progression through S-phase. Taylor & Francis 2015-12-22 /pmc/articles/PMC4889237/ /pubmed/26694751 http://dx.doi.org/10.1080/15384101.2015.1128597 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Report
Bailey, Laura J.
Bianchi, Julie
Hégarat, Nadia
Hochegger, Helfrid
Doherty, Aidan J.
PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage
title PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage
title_full PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage
title_fullStr PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage
title_full_unstemmed PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage
title_short PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage
title_sort primpol-deficient cells exhibit a pronounced g2 checkpoint response following uv damage
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889237/
https://www.ncbi.nlm.nih.gov/pubmed/26694751
http://dx.doi.org/10.1080/15384101.2015.1128597
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