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DNA Repair (Amst) ; 93: 102913, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33087279

RESUMO

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 ∼80 % 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.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Proteína Homóloga a MRE11/metabolismo , Radiação Ionizante , Reparo de DNA por Recombinação , Ciclo Celular , DNA/metabolismo , DNA/efeitos da radiação , Adutos de DNA/metabolismo , DNA Ligase Dependente de ATP/metabolismo , Humanos
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