Spatiotemporal regulation of DNA repair proteins between Golgi and nucleus maintains genome stability.

Authors

George Galea, Karolina Kuodyte, Muzamil Majid Khan, Peter J Thul, Beate Neumann, Emma Lundberg, Rainer Pepperkok

Published in

The Journal of cell biology. Volume 225. Issue 9. Sep 07, 2026. Epub Jul 28, 2026.

Abstract

The Golgi complex serves as a critical hub for cellular homeostasis, yet its communication with the nucleus remains largely unexplored. 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)-dependent release of a giantin-tethered Golgi RAD51C pool, with subsequent importin-β-dependent 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.

PMID:
42517872
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.

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