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
em 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Precursores de RNA
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Reparo do DNA
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Proteína Quinase Ativada por DNA
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Quebras de DNA de Cadeia Dupla
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Autoantígeno Ku
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China