A Mechanism to Minimize Errors during Non-homologous End Joining.
Mol Cell
; 77(5): 1080-1091.e8, 2020 03 05.
Article
em En
| MEDLINE
| ID: mdl-31862156
ABSTRACT
Enzymatic processing of DNA underlies all DNA repair, yet inappropriate DNA processing must be avoided. In vertebrates, double-strand breaks are repaired predominantly by non-homologous end joining (NHEJ), which directly ligates DNA ends. NHEJ has the potential to be highly mutagenic because it uses DNA polymerases, nucleases, and other enzymes that modify incompatible DNA ends to allow their ligation. Using frog egg extracts that recapitulate NHEJ, we show that end processing requires the formation of a "short-range synaptic complex" in which DNA ends are closely aligned in a ligation-competent state. Furthermore, single-molecule imaging directly demonstrates that processing occurs within the short-range complex. This confinement of end processing to a ligation-competent complex ensures that DNA ends undergo ligation as soon as they become compatible, thereby minimizing mutagenesis. Our results illustrate how the coordination of enzymatic catalysis with higher-order structural organization of substrate maximizes the fidelity of DNA repair.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Instabilidade Genômica
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Quebras de DNA de Cadeia Dupla
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Reparo do DNA por Junção de Extremidades
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article