DNA damage-induced inhibition of rRNA synthesis by DNA-PK and PARP-1.
Nucleic Acids Res
; 41(15): 7378-86, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23775790
ABSTRACT
RNA synthesis and DNA replication cease after DNA damage. We studied RNA synthesis using an in situ run-on assay and found ribosomal RNA (rRNA) synthesis was inhibited 24 h after UV light, gamma radiation or DNA cross-linking by cisplatin in human cells. Cisplatin led to accumulation of cells in S phase. Inhibition of the DNA repair proteins DNA-dependent protein kinase (DNA-PK) or poly(ADP-ribose) polymerase 1 (PARP-1) prevented the DNA damage-induced block of rRNA synthesis. However, DNA-PK and PARP-1 inhibition did not prevent the cisplatin-induced arrest of cell cycle in S phase, nor did it induce de novo BrdU incorporation. Loss of DNA-PK function prevented activation of PARP-1 and its recruitment to chromatin in damaged cells, suggesting regulation of PARP-1 by DNA-PK within a pathway of DNA repair. From these results, we propose a sequential activation of DNA-PK and PARP-1 in cells arrested in S phase by DNA damage causes the interruption of rRNA synthesis after DNA damage.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
RNA Ribossômico
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Proteínas Nucleares
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Poli(ADP-Ribose) Polimerases
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Proteína Quinase Ativada por DNA
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos