Authors
Javier Rodríguez González, Olivia T Herman, Kaden E Lewis, Lindsay A Matthews, Luke D Hess, Jennifer A Surtees, Alba Guarné
Published in
Nucleic acids research. Volume 54. Issue 17. Sep 07, 2026.
Abstract
Saccharomyces cerevisiae Rad1-Rad10 (XPF-ERCC1 in humans) is a 3'-flap endonuclease with key roles in DNA repair. Pathway-specific repair factors determine its recruitment to specific DNA substrates. Saw1 recruits it to 3' non-homologous tail recombination intermediates, while Rad14 recruits it to UV-lesions repaired by nucleotide excision repair. However, the exact recruitment mechanisms are unknown. We determined the cryo-EM structure of the Rad1-Rad10-Saw1 complex at 3.7 Å resolution. The structure reveals that Saw1 wraps around the helicase-like domain of Rad1 defining an extensive interface. Point mutations on this surface disrupt the interaction and inhibit double-strand break repair without compromising nucleotide excision repair, indicating that Rad1-Rad10 uses different surfaces to interact with pathway-specific repair factors. Mutational analyses confirm that Rad14 and Saw1 bind to opposite faces of Rad1. Accordingly, defects on the Rad14-binding interface disrupt nucleotide excision repair without affecting double-strand break repair. In contrast to XPF-ERCC1, Rad1-Rad10 does not adopt an auto-inhibited conformation in the absence of DNA indicating that substrate binding may be regulated differently across species. Collectively, our data provide structural insight into how targeting factors interact with Rad1-Rad10 to recruit it to different DNA repair intermediates.
PMID:
42745665
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.
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