DNA-PK participates in pre-rRNA biogenesis independent of DNA double-strand break repair.
Nucleic Acids Res
; 52(11): 6360-6375, 2024 Jun 24.
Article
in En
| MEDLINE
| ID: mdl-38682589
ABSTRACT
Although DNA-PK inhibitors (DNA-PK-i) have been applied in clinical trials for cancer treatment, the biomarkers and mechanism of action of DNA-PK-i in tumor cell suppression remain unclear. Here, we observed that a low dose of DNA-PK-i and PARP inhibitor (PARP-i) synthetically suppresses BRCA-deficient tumor cells without inducing DNA double-strand breaks (DSBs). Instead, we found that a fraction of DNA-PK localized inside of nucleoli, where we did not observe obvious DSBs. Moreover, the Ku proteins recognize pre-rRNA that facilitates DNA-PKcs autophosphorylation independent of DNA damage. Ribosomal proteins are also phosphorylated by DNA-PK, which regulates pre-rRNA biogenesis. In addition, DNA-PK-i acts together with PARP-i to suppress pre-rRNA biogenesis and tumor cell growth. Collectively, our studies reveal a DNA damage repair-independent role of DNA-PK-i in tumor suppression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA Precursors
/
DNA Repair
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DNA-Activated Protein Kinase
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DNA Breaks, Double-Stranded
/
Ku Autoantigen
Limits:
Animals
/
Humans
Language:
En
Journal:
Nucleic Acids Res
Year:
2024
Document type:
Article
Affiliation country: