ELL2 regulates DNA non-homologous end joining (NHEJ) repair in prostate cancer cells.
Cancer Lett
; 415: 198-207, 2018 02 28.
Article
em En
| MEDLINE
| ID: mdl-29179998
ELL2 is an androgen-responsive gene that is expressed by prostate epithelial cells and is frequently down-regulated in prostate cancer. Deletion of Ell2 in the murine prostate induced murine prostatic intraepithelial neoplasia and ELL2 knockdown enhanced proliferation and migration in C4-2 prostate cancer cells. Here, knockdown of ELL2 sensitized prostate cancer cells to DNA damage and overexpression of ELL2 protected prostate cancer cells from DNA damage. Knockdown of ELL2 impaired non-homologous end joining repair but not homologous recombination repair. Transfected ELL2 co-immunoprecipitated with both Ku70 and Ku80 proteins. ELL2 could bind to and co-accumulate with Ku70/Ku80 proteins at sites of DNA damage. Knockdown of ELL2 dramatically inhibited Ku70 and Ku80 recruitment and retention at DNA double-strand break sites in prostate cancer cells. The impaired recruitment of Ku70 and Ku80 proteins to DNA damage sites upon ELL2 knockdown was rescued by re-expression of an ELL2 transgene insensitive to siELL2. This study suggests that ELL2 is required for efficient NHEJ repair via Ku70/Ku80 in prostate cancer cells.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Elongação da Transcrição
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Interferência de RNA
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Reparo do DNA
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Reparo do DNA por Junção de Extremidades
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article