Transcriptional Regulation at DSBs: Mechanisms and Consequences.
Trends Genet
; 36(12): 981-997, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-32001024
ABSTRACT
Defective double-strand break (DSB) repair leads to genomic instabilities that may augment carcinogenesis. DSBs trigger transient transcriptional silencing in the vicinity of transcriptionally active genes through multilayered processes instigated by Ataxia telangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK), and poly-(ADP-ribose) polymerase 1 (PARP1). Novel factors have been identified that ensure DSB-induced silencing via two distinct pathways direct inhibition of RNA Polymerase II (Pol II) mediated by negative elongation factor (NELF), and histone code editing by CDYL1 and histone deacetylases (HDACs) that catalyze H3K27me3 and erase lysine crotonylation, respectively. Here, we highlight major advances in understanding the mechanisms underlying transcriptional silencing at DSBs, and discuss its functional implications on repair. Furthermore, we discuss consequential links between DSB-silencing factors and carcinogenesis and discuss the potential of exploiting them for targeted cancer therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Regulação Neoplásica da Expressão Gênica
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Instabilidade Genômica
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Proteínas de Ligação a DNA
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Reparo do DNA
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Quebras de DNA de Cadeia Dupla
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Trends Genet
Assunto da revista:
GENETICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Israel