Restoration of ligatable "clean" double-strand break ends is the rate-limiting step in the rejoining of ionizing-radiation-induced DNA breakage.
DNA Repair (Amst)
; 93: 102913, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-33087279
ABSTRACT
Radiotherapy kills malignant cells by generating double-strand breaks (DSBs). Ionizing- radiation (IR) generates "dirty" DSBs, which associates with blocking chemical adducts at DSB ends. Homologous-directed repair (HDR) efficiently removes IR-induced blocking adducts from both 3' and 5' ends of DSBs. Nonhomologous end-joining (NHEJ) rejoins virtually all DSBs in G1 phase and â¼80 % of DSBs in G2 phase. However, DNA Ligase IV, an essential NHEJ factor, rejoins only "clean" ligatable DSBs carrying 3'-OH and 5'-phosphate DSB ends but not dirty DSBs. Recent studies have identified a number of nucleases, especially the MRE11 nuclease, as key factors performing the removal of blocking chemical adducts to restore clean ligatable DSBs for subsequent NHEJ. This restoration, but not subsequent NHEJ, is the rate-limiting step in the rejoining of IR- induced DSBs. This review describes repair factors that contribute to the restoration of clean DSBs before NHEJ.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiação Ionizante
/
Quebras de DNA de Cadeia Dupla
/
Reparo do DNA por Junção de Extremidades
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Reparo de DNA por Recombinação
/
Proteína Homóloga a MRE11
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
DNA Repair (Amst)
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão