Implication of E3 ligase RAD18 in UV-induced mutagenesis in human induced pluripotent stem cells and neuronal progenitor cells.
RAD18
UV exposure
induced pluripotent stem cells (iPSCs)
mutation frequency
Journal
Journal of radiation research
ISSN: 1349-9157
Titre abrégé: J Radiat Res
Pays: England
ID NLM: 0376611
Informations de publication
Date de publication:
23 Mar 2023
23 Mar 2023
Historique:
received:
11
10
2022
revised:
24
11
2022
accepted:
03
12
2022
pubmed:
13
1
2023
medline:
28
3
2023
entrez:
12
1
2023
Statut:
ppublish
Résumé
Pluripotent stem cells (PSCs) have the potential to differentiate to any of the other organs. The genome DNA integrity of PSCs is maintained by a high level of transcription for a number of genes involved in DNA repair, cell cycle and apoptosis. However, it remains unclear how high the frequency of genetic mutation is and how these DNA repair factors function in PSCs. In this study, we employed Sup F assay for the measurement of mutation frequency after UV-C irradiation in induced pluripotent stem cells (iPSCs) as PSC models and neural progenitor cells (NPCs) were derived from iPSCs as differentiated cells. iPSCs and NPCs exhibited a lower mutation frequency compared with the original skin fibroblasts. In RNA-seq analysis, iPSCs and NPCs showed a high expression of RAD18, which is involved in trans-lesion synthesis (TLS) for the emergency tolerance system during the replication process of DNA. Although RAD18 is involved in both error free and error prone TLS in somatic cells, it still remains unknown the function of RAD18 in PSCs. In this study we depleted of the RAD18 by siRNA knockdown resulted in decreased frequency of mutation in iPSCs and NPCs. Our results will provide information on the genome maintenance machinery in PSCs.
Identifiants
pubmed: 36634340
pii: 6984803
doi: 10.1093/jrr/rrac099
pmc: PMC10036092
doi:
Substances chimiques
Ubiquitin-Protein Ligases
EC 2.3.2.27
RAD18 protein, human
0
DNA-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
345-351Subventions
Organisme : Chubu Electric Power Company [to MS], Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science
ID : JP21K19842
Organisme : JAEA Nuclear Energy S&T and Human Resource Development Project
ID : JPJA18B18071955
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.
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