Mammalian life depends on two distinct pathways of DNA damage tolerance.
DNA damage response (DDR)
DNA damage tolerance (DDT)
embryonic lethality
erythropoiesis
hematopoietic stem cells
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
24 Jan 2023
24 Jan 2023
Historique:
entrez:
20
1
2023
pubmed:
21
1
2023
medline:
25
1
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36669105
doi: 10.1073/pnas.2216055120
pmc: PMC9942833
doi:
Substances chimiques
Proliferating Cell Nuclear Antigen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2216055120Subventions
Organisme : KWF Kankerbestrijding (DCS)
ID : 10032
Organisme : KWF Kankerbestrijding (DCS)
ID : 10796
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