Small Cajal body-associated RNA 2 (scaRNA2) regulates DNA repair pathway choice by inhibiting DNA-PK.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 02 2022
23 02 2022
Historique:
received:
01
04
2021
accepted:
25
01
2022
entrez:
24
2
2022
pubmed:
25
2
2022
medline:
13
4
2022
Statut:
epublish
Résumé
Evidence that long non-coding RNAs (lncRNAs) participate in DNA repair is accumulating, however, whether they can control DNA repair pathway choice is unknown. Here we show that the small Cajal body-specific RNA 2 (scaRNA2) can promote HR by inhibiting DNA-dependent protein kinase (DNA-PK) and, thereby, NHEJ. By binding to the catalytic subunit of DNA-PK (DNA-PKcs), scaRNA2 weakens its interaction with the Ku70/80 subunits, as well as with the LINP1 lncRNA, thereby preventing catalytic activation of the enzyme. Inhibition of DNA-PK by scaRNA2 stimulates DNA end resection by the MRN/CtIP complex, activation of ATM at DNA lesions and subsequent repair by HR. ScaRNA2 is regulated in turn by WRAP53β, which binds this RNA, sequestering it away from DNA-PKcs and allowing NHEJ to proceed. These findings reveal that RNA-dependent control of DNA-PK catalytic activity is involved in regulating whether the cell utilizes NHEJ or HR.
Identifiants
pubmed: 35197472
doi: 10.1038/s41467-022-28646-5
pii: 10.1038/s41467-022-28646-5
pmc: PMC8866460
doi:
Substances chimiques
DNA-Binding Proteins
0
RNA
63231-63-0
DNA
9007-49-2
Protein Kinases
EC 2.7.-
DNA-Activated Protein Kinase
EC 2.7.11.1
Ku Autoantigen
EC 4.2.99.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1015Informations de copyright
© 2022. The Author(s).
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