Mammalian life depends on two distinct pathways of DNA damage tolerance

DNA damage threatens genomic integrity and instigates stem cell failure. To bypass genotoxic lesions during replication, cells employ DNA damage tolerance (DDT), which is regulated via PCNA ubiquitination and REV1. DDT is conserved in all domains of life, yet its relevance in mammals remains unclear...

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Autores principales: Buoninfante, Olimpia Alessandra, Pilzecker, Bas, Spanjaard, Aldo, de Groot, Daniël, Prekovic, Stefan, Song, Ji-Ying, Lieftink, Cor, Ayidah, Matilda, Pritchard, Colin E. J., Vivié, Judith, Mcgrath, Kathleen E., Huijbers, Ivo J., Philipsen, Sjaak, von Lindern, Marieke, Zwart, Wilbert, Beijersbergen, Roderick L., Palis, James, van den Berk, Paul C. M., Jacobs, Heinz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Biological Sciences
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942833/
https://www.ncbi.nlm.nih.gov/pubmed/36669105
http://dx.doi.org/10.1073/pnas.2216055120
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author Buoninfante, Olimpia Alessandra
Pilzecker, Bas
Spanjaard, Aldo
de Groot, Daniël
Prekovic, Stefan
Song, Ji-Ying
Lieftink, Cor
Ayidah, Matilda
Pritchard, Colin E. J.
Vivié, Judith
Mcgrath, Kathleen E.
Huijbers, Ivo J.
Philipsen, Sjaak
von Lindern, Marieke
Zwart, Wilbert
Beijersbergen, Roderick L.
Palis, James
van den Berk, Paul C. M.
Jacobs, Heinz
author_facet Buoninfante, Olimpia Alessandra
Pilzecker, Bas
Spanjaard, Aldo
de Groot, Daniël
Prekovic, Stefan
Song, Ji-Ying
Lieftink, Cor
Ayidah, Matilda
Pritchard, Colin E. J.
Vivié, Judith
Mcgrath, Kathleen E.
Huijbers, Ivo J.
Philipsen, Sjaak
von Lindern, Marieke
Zwart, Wilbert
Beijersbergen, Roderick L.
Palis, James
van den Berk, Paul C. M.
Jacobs, Heinz
author_sort Buoninfante, Olimpia Alessandra
collection PubMed
description DNA damage threatens genomic integrity and instigates stem cell failure. To bypass genotoxic lesions during replication, cells employ DNA damage tolerance (DDT), which is regulated via PCNA ubiquitination and REV1. DDT is conserved in all domains of life, yet its relevance in mammals remains unclear. Here, we show that inactivation of both PCNA-ubiquitination and REV1 results in embryonic and adult lethality, and the accumulation of DNA damage in hematopoietic stem and progenitor cells (HSPCs) that ultimately resulted in their depletion. Our results reveal the crucial relevance of DDT in the maintenance of stem cell compartments and mammalian life in unperturbed conditions.
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spelling pubmed-99428332023-02-22 Mammalian life depends on two distinct pathways of DNA damage tolerance Buoninfante, Olimpia Alessandra Pilzecker, Bas Spanjaard, Aldo de Groot, Daniël Prekovic, Stefan Song, Ji-Ying Lieftink, Cor Ayidah, Matilda Pritchard, Colin E. J. Vivié, Judith Mcgrath, Kathleen E. Huijbers, Ivo J. Philipsen, Sjaak von Lindern, Marieke Zwart, Wilbert Beijersbergen, Roderick L. Palis, James van den Berk, Paul C. M. Jacobs, Heinz Proc Natl Acad Sci U S A Biological Sciences DNA damage threatens genomic integrity and instigates stem cell failure. To bypass genotoxic lesions during replication, cells employ DNA damage tolerance (DDT), which is regulated via PCNA ubiquitination and REV1. DDT is conserved in all domains of life, yet its relevance in mammals remains unclear. Here, we show that inactivation of both PCNA-ubiquitination and REV1 results in embryonic and adult lethality, and the accumulation of DNA damage in hematopoietic stem and progenitor cells (HSPCs) that ultimately resulted in their depletion. Our results reveal the crucial relevance of DDT in the maintenance of stem cell compartments and mammalian life in unperturbed conditions. National Academy of Sciences 2023-01-20 2023-01-24 /pmc/articles/PMC9942833/ /pubmed/36669105 http://dx.doi.org/10.1073/pnas.2216055120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Buoninfante, Olimpia Alessandra
Pilzecker, Bas
Spanjaard, Aldo
de Groot, Daniël
Prekovic, Stefan
Song, Ji-Ying
Lieftink, Cor
Ayidah, Matilda
Pritchard, Colin E. J.
Vivié, Judith
Mcgrath, Kathleen E.
Huijbers, Ivo J.
Philipsen, Sjaak
von Lindern, Marieke
Zwart, Wilbert
Beijersbergen, Roderick L.
Palis, James
van den Berk, Paul C. M.
Jacobs, Heinz
Mammalian life depends on two distinct pathways of DNA damage tolerance
title Mammalian life depends on two distinct pathways of DNA damage tolerance
title_full Mammalian life depends on two distinct pathways of DNA damage tolerance
title_fullStr Mammalian life depends on two distinct pathways of DNA damage tolerance
title_full_unstemmed Mammalian life depends on two distinct pathways of DNA damage tolerance
title_short Mammalian life depends on two distinct pathways of DNA damage tolerance
title_sort mammalian life depends on two distinct pathways of dna damage tolerance
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942833/
https://www.ncbi.nlm.nih.gov/pubmed/36669105
http://dx.doi.org/10.1073/pnas.2216055120
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