ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition.
Nucleic Acids Res
; 49(20): 11666-11689, 2021 11 18.
Article
em En
| MEDLINE
| ID: mdl-34718742
ABSTRACT
The inhibitor of DNA-binding 3 (ID3) is a transcriptional regulator that limits interaction of basic helix-loop-helix transcription factors with their target DNA sequences. We previously reported that ID3 loss is associated with mutational signatures linked to DNA repair defects. Here we demonstrate that ID3 exhibits a dual role to promote DNA double-strand break (DSB) repair, particularly homologous recombination (HR). ID3 interacts with the MRN complex and RECQL helicase to activate DSB repair and it facilitates RAD51 loading and downstream steps of HR. In addition, ID3 promotes the expression of HR genes in response to ionizing radiation by regulating both chromatin accessibility and activity of the transcription factor E2F1. Consistently, analyses of TCGA cancer patient data demonstrate that low ID3 expression is associated with impaired HR. The loss of ID3 leads to sensitivity of tumor cells to PARP inhibition, offering new therapeutic opportunities in ID3-deficient tumors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Proteínas Inibidoras de Diferenciação
/
Recombinação Homóloga
/
Proteínas de Neoplasias
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha