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NHEJ is capable of repairing a variety of damaged DNA, employing various accessory end-processing factors to resolve chemically blocked ends, trim overhangs, and fill gaps in order to achieve directly ligatable DNA ends. To investigate the molecular mechanisms underlying end-processing, we determine the cryo-EM structure of the NHEJ specific polymerase Pol \u03bb bound to the short-range synaptic complex, detailing the mode of its recruitment to the complex as well as a putative model for its activity. Furthermore, the coordinated end-processing activities of the short-range (SR) synaptic complex simultaneously bound by both Pol \u03bb and PNKP, another accessory factor, demonstrates the ability of NHEJ to form large, multifunctional repair complexes capable of processing a variety of different DNA end structures to effect repair.<\/jats:p>","DOI":"10.1038\/s41467-026-77503-2","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:15:01Z","timestamp":1788916501000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["End processing in NHEJ by Polymerase \u03bb and PNKP is coordinated during short-range synapsis"],"prefix":"10.1038","volume":"17","author":[{"given":"Alex","family":"Vogt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-4186","authenticated-orcid":false,"given":"Andrea M.","family":"Kaminski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason G.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasmin","family":"Naila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3041-1620","authenticated-orcid":false,"given":"Danny","family":"Laurent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2671-1711","authenticated-orcid":false,"given":"Alan E.","family":"Tomkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5809-2516","authenticated-orcid":false,"given":"Susan P.","family":"Lees-Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-4077","authenticated-orcid":false,"given":"Lars C.","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9900-1788","authenticated-orcid":false,"given":"Thomas A.","family":"Kunkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-3963","authenticated-orcid":false,"given":"Yuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"77503_CR1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1146\/annurev-biochem-080320-110356","volume":"90","author":"BM Stinson","year":"2021","unstructured":"Stinson, B. 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