Cryo-EM of NHEJ supercomplexes provides insights into DNA repair.
Mol Cell
; 81(16): 3400-3409.e3, 2021 08 19.
Article
em En
| MEDLINE
| ID: mdl-34352203
ABSTRACT
Non-homologous end joining (NHEJ) is one of two critical mechanisms utilized in humans to repair DNA double-strand breaks (DSBs). Unrepaired or incorrect repair of DSBs can lead to apoptosis or cancer. NHEJ involves several proteins, including the Ku70/80 heterodimer, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), X-ray cross-complementing protein 4 (XRCC4), XRCC4-like factor (XLF), and ligase IV. These core proteins bind DSBs and ligate the damaged DNA ends. However, details of the structural assembly of these proteins remain unclear. Here, we present cryo-EM structures of NHEJ supercomplexes that are composed of these core proteins and DNA, revealing the detailed structural architecture of this assembly. We describe monomeric and dimeric forms of this supercomplex and also propose the existence of alternate dimeric forms of long-range synaptic complexes. Finally, we show that mutational disruption of several structural features within these NHEJ complexes negatively affects DNA repair.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Enzimas Reparadoras do DNA
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Complexos Multiproteicos
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Proteínas de Ligação a DNA
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Proteína Quinase Ativada por DNA
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DNA Ligase Dependente de ATP
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article