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TitleCryo-EM of NHEJ supercomplexes provides insights into DNA repair.
Journal, issue, pagesMol Cell, Vol. 81, Issue 16, Page 3400-33409.e3, Year 2021
Publish dateAug 19, 2021
AuthorsAmanda K Chaplin / Steven W Hardwick / Antonia Kefala Stavridi / Christopher J Buehl / Noah J Goff / Virginie Ropars / Shikang Liang / Taiana Maia De Oliveira / Dimitri Y Chirgadze / Katheryn Meek / Jean-Baptiste Charbonnier / Tom L Blundell /
PubMed AbstractNon-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 ...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.
External linksMol Cell / PubMed:34352203 / PubMed Central
MethodsEM (single particle)
Resolution4.14 - 4.29 Å
Structure data

12299

7nfc

EMDB-12299, PDB-7nfc:
Cryo-EM structure of NHEJ super-complex (dimer)
Method: EM (single particle) / Resolution: 4.14 Å

12301

7nfe

EMDB-12301, PDB-7nfe:
Cryo-EM structure of NHEJ super-complex (monomer)
Method: EM (single particle) / Resolution: 4.29 Å

Source
  • homo sapiens (human)
  • Human (human)
KeywordsDNA BINDING PROTEIN / NHEJ / DNA-PKcs / Ku70/80 / XLF / XRCC4 / DNA-LigaseIV

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