{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen S"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["eadg2838"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10413680"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(22)"],"pubmed_abstract":["DNA double-strand breaks (DSBs), one of the most cytotoxic forms of DNA damage, can be repaired by the tightly regulated nonhomologous end joining (NHEJ) machinery (Stinson and Loparo and Zhao <i>et al.</i>). Core NHEJ factors form an initial long-range (LR) synaptic complex that transitions into a DNA-PKcs (DNA-dependent protein kinase, catalytic subunit)-free, short-range state to align the DSB ends (Chen <i>et al.</i>). Using single-particle cryo-electron microscopy, we have visualized three additional key NHEJ complexes representing different transition states, with DNA-PKcs adopting distinct dimeric conformations within each of them. Upon DNA-PKcs autophosphorylation, the LR complex undergoes a substantial conformational change, with both Ku and DNA-PKcs rotating outward to promote DN"],"journal":["Science advances"],"pubmed_title":["Cryo-EM visualization of DNA-PKcs structural intermediates in NHEJ."],"pmcid":["PMC10413680"],"funding_grant_id":["R01 GM144559","T32 GM008382","U24 GM129547","P30 CA060553","R01 GM047251","P01 CA092584","P30 CA118100","R01 GM135651","T32 GM140995"],"pubmed_authors":["McKeown R","He Y","Lee L","Tomkinson AE","Naila T","Vogt A","Lees-Miller SP","Chen S"],"additional_accession":[]},"is_claimable":false,"name":"Cryo-EM visualization of DNA-PKcs structural intermediates in NHEJ.","description":"DNA double-strand breaks (DSBs), one of the most cytotoxic forms of DNA damage, can be repaired by the tightly regulated nonhomologous end joining (NHEJ) machinery (Stinson and Loparo and Zhao <i>et al.</i>). Core NHEJ factors form an initial long-range (LR) synaptic complex that transitions into a DNA-PKcs (DNA-dependent protein kinase, catalytic subunit)-free, short-range state to align the DSB ends (Chen <i>et al.</i>). Using single-particle cryo-electron microscopy, we have visualized three additional key NHEJ complexes representing different transition states, with DNA-PKcs adopting distinct dimeric conformations within each of them. Upon DNA-PKcs autophosphorylation, the LR complex undergoes a substantial conformational change, with both Ku and DNA-PKcs rotating outward to promote DN","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jun","modification":"2026-05-29T07:39:02.307Z","creation":"2025-02-19T01:18:12.331Z"},"accession":"S-EPMC10413680","cross_references":{"pubmed":["37256947"],"doi":["10.1126/sciadv.adg2838"]}}