7NFE

Cryo-EM structure of NHEJ super-complex (monomer)

Summary for 7NFE

• Entry DOI: 10.2210/pdb7nfe/pdb
• EMDB information: 12301
• Descriptor: DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit, X-ray repair cross-complementing protein 6, X-ray repair cross-complementing protein 5, ... (8 entities in total)
• Functional Keywords: nhej, dna-pkcs, ku70/80, xlf, xrcc4, dna-ligaseiv, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 887129.25

Authors

Chaplin, A.K.,Hardwick, S.W.,Kefala Stavridi, A.,Chirgadze, D.Y.,Blundell, T.L. (deposition date: 2021-02-06, release date: 2021-08-18, Last modification date: 2024-07-10)

Primary citation

Chaplin, A.K.,Hardwick, S.W.,Stavridi, A.K.,Buehl, C.J.,Goff, N.J.,Ropars, V.,Liang, S.,De Oliveira, T.M.,Chirgadze, D.Y.,Meek, K.,Charbonnier, J.B.,Blundell, T.L.
Cryo-EM of NHEJ supercomplexes provides insights into DNA repair.
Mol.Cell, 81:3400-3409, 2021

PubMed 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.

PubMed: 34352203
DOI: 10.1016/j.molcel.2021.07.005

Experimental method

ELECTRON MICROSCOPY (4.29 Å)