Lysines 3241 and 3260 of DNA-PKcs are important for genomic stability and radioresistance.
Biochem Biophys Res Commun
; 477(2): 235-40, 2016 08 19.
Article
em En
| MEDLINE
| ID: mdl-27297111
ABSTRACT
DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase that plays an essential role in the repair of DNA double-strand breaks (DSBs) in the non-homologous end-joining (NHEJ) pathway. The DNA-PK holoenzyme consists of a catalytic subunit (DNA-PKcs) and DNA-binding subunit (Ku70/80, Ku). Ku is a molecular sensor for double-stranded DNA and once bound to DSB ends it recruits DNA-PKcs to the DSB site. Subsequently, DNA-PKcs is activated and heavily phosphorylated, with these phosphorylations modulating DNA-PKcs. Although phosphorylation of DNA-PKcs is well studied, other post-translational modifications of DNA-PKcs are not. In this study, we aimed to determine if acetylation of DNA-PKcs regulates DNA-PKcs-dependent DSB repair. We report that DNA-PKcs is acetylated in vivo and identified two putative acetylation sites, lysine residues 3241 and 3260. Mutating these sites to block potential acetylation results in increased radiosensitive, a slight decrease in DSB repair capacity as assessed by γH2AX resolution, and increased chromosomal aberrations, especially quadriradial chromosomes. Together, our results provide evidence that acetylation potentially regulates DNA-PKcs.
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MEDLINE
Assunto principal:
Tolerância a Radiação
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Dano ao DNA
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DNA
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Proteínas Nucleares
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Instabilidade Genômica
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Proteína Quinase Ativada por DNA
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article