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By analyzing and siRNA-validating localization data from the Human Protein Atlas, we uncovered substantial proteome interconnectivity between the Golgi and nucleus, including an unexpected enrichment for DNA repair factors. We identify a cluster of DNA damage response (DDR) proteins occupying distinct sub-Golgi compartments that redistribute dynamically between the Golgi and nucleus in response to genotoxic stress, with the type of DNA lesion shaping the direction of redistribution. Focusing on the homologous recombination (HR) regulator RAD51C, we show that DNA damage triggers ataxia telangiectasia mutated (ATM)\u2013dependent release of a giantin-tethered Golgi RAD51C pool, with subsequent importin-\u03b2\u2013dependent nuclear import, where repair-associated foci form. Giantin depletion prematurely releases RAD51C, producing aberrant nuclear foci lacking key DDR markers, reducing ATM activation and HR efficiency, elevating genome instability, and accelerating proliferation. The Golgi thus acts as a spatiotemporal coordination node for DDR factors safeguarding genomic stability.<\/jats:p>","DOI":"10.1083\/jcb.202605024","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T06:21:24Z","timestamp":1781331684000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal regulation of DNA repair proteins between Golgi and nucleus maintains genome stability"],"prefix":"10.1083","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-2726","authenticated-orcid":true,"given":"George","family":"Galea","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mstc592","id-type":"ROR","asserted-by":"publisher"}],"name":"Cell Biology and Biophysics Unit, European Molecular Biology Laboratory 1 , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9677-549X","authenticated-orcid":true,"given":"Karolina","family":"Kuodyte","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mstc592","id-type":"ROR","asserted-by":"publisher"}],"name":"Cell Biology and Biophysics Unit, European Molecular Biology Laboratory 1 , Heidelberg,","place":["Germany"]},{"name":"Collaboration for Joint PhD Degree Between European Molecular Biology Laboratory and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8188-0251","authenticated-orcid":true,"given":"Muzamil Majid","family":"Khan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mstc592","id-type":"ROR","asserted-by":"publisher"}],"name":"Cell Biology and Biophysics Unit, European Molecular Biology Laboratory 1 , Heidelberg,","place":["Germany"]},{"name":"Translational Lung Research Center Heidelberg, German Center for Lung Research 3 , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6107-1465","authenticated-orcid":true,"given":"Peter J.","family":"Thul","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/026vcq606","id-type":"ROR","asserted-by":"publisher"}],"name":"Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of Technology 4 , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6899-502X","authenticated-orcid":true,"given":"Beate","family":"Neumann","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory 5 Advanced Light Microscopy Facility, , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7034-0850","authenticated-orcid":true,"given":"Emma","family":"Lundberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/026vcq606","id-type":"ROR","asserted-by":"publisher"}],"name":"Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of Technology 4 , Stockholm,","place":["Sweden"]},{"name":"Stanford University 6 Department of Bioengineering, , Stanford, CA,","place":["USA"]},{"name":"Stanford University 7 Department of Pathology, , Stanford, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9762-3583","authenticated-orcid":true,"given":"Rainer","family":"Pepperkok","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mstc592","id-type":"ROR","asserted-by":"publisher"}],"name":"Cell Biology and Biophysics Unit, European Molecular Biology Laboratory 1 , Heidelberg,","place":["Germany"]},{"name":"Translational Lung Research Center Heidelberg, German Center for Lung Research 3 , Heidelberg,","place":["Germany"]},{"name":"European Molecular Biology Laboratory 5 Advanced Light Microscopy Facility, , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"2026072809453882200_bib1","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/ncb2426","article-title":"A genome-wide homologous recombination screen identifies the RNA-Binding protein RBMX as a component of the DNA-damage response","volume":"14","author":"Adamson","year":"2012","journal-title":"Nat. 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