TENT4A Non-Canonical Poly(A) Polymerase Regulates DNA-Damage Tolerance via Multiple Pathways That Are Mutated in Endometrial Cancer.
Blotting, Western
Cell Line, Tumor
Chromosomal Proteins, Non-Histone
/ genetics
Computational Biology
DNA Damage
/ genetics
DNA Repair
/ genetics
DNA Replication
/ genetics
DNA-Binding Proteins
/ genetics
DNA-Directed DNA Polymerase
/ genetics
Endometrial Neoplasms
/ genetics
Female
HEK293 Cells
Humans
Immunoprecipitation
MCF-7 Cells
Mutation
/ genetics
Polymerase Chain Reaction
Polynucleotide Adenylyltransferase
/ genetics
RNA Stability
/ genetics
RNA, Messenger
/ genetics
Ubiquitin-Protein Ligases
/ genetics
Ubiquitination
/ genetics
DNA repair
TLS
lesion bypass
poly(A) RNA polymerase
translesion
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
28 Jun 2021
28 Jun 2021
Historique:
received:
25
04
2021
revised:
20
06
2021
accepted:
21
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
3
8
2021
Statut:
epublish
Résumé
TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here, we show that TENT4A regulates multiple biological pathways and focuses on its multilayer regulation of translesion DNA synthesis (TLS), in which error-prone DNA polymerases bypass unrepaired DNA lesions. We show that TENT4A regulates mRNA stability and/or translation of DNA polymerase η and RAD18 E3 ligase, which guides the polymerase to replication stalling sites and monoubiquitinates PCNA, thereby enabling recruitment of error-prone DNA polymerases to damaged DNA sites. Remarkably, in addition to the effect on RAD18 mRNA stability via controlling its poly(A) tail, TENT4A indirectly regulates RAD18 via the tumor suppressor CYLD and via the long non-coding antisense RNA
Identifiants
pubmed: 34203408
pii: ijms22136957
doi: 10.3390/ijms22136957
pmc: PMC8267958
pii:
doi:
Substances chimiques
Chromosomal Proteins, Non-Histone
0
DNA-Binding Proteins
0
PAXIP1 protein, human
0
RAD18 protein, human
0
RNA, Messenger
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Polynucleotide Adenylyltransferase
EC 2.7.7.19
DNA-Directed DNA Polymerase
EC 2.7.7.7
TENT4A protein, human
EC 2.7.7.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Israel Science Foundation
ID : 684/12
Organisme : Minerva Foundation
ID : 120855
Organisme : Flight Attendant Medical Research Institute
ID : 032001
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