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TitleMolecular basis of XPF-ERCC1 targeting to SLX4-dependent DNA repair pathways.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Page 522, Year 2025
Publish dateDec 16, 2025
AuthorsJunjie Feng / Peter R Martin / Szymon Kowalski / Maxime Lecot / Nora B Cronin / Teige Matthews-Palmer / Wojciech Niedzwiedz / Basil J Greber /
PubMed AbstractThe preservation and faithful propagation of genetic information is essential for all life forms and depends on cellular pathways that enable replication, recombination, and repair of DNA. The ...The preservation and faithful propagation of genetic information is essential for all life forms and depends on cellular pathways that enable replication, recombination, and repair of DNA. The multifunctional XPF-ERCC1 DNA endonuclease complex acts in several DNA repair pathways and interacts with numerous partner proteins and large DNA repair assemblies, including the nucleotide excision repair machinery and the SMX tri-endonuclease complex. Here, we report structures of XPF-ERCC1 in complex with the DNA repair factors SLX4 and SLX4IP, thereby identifying key residues responsible for direct interactions with XPF-ERCC1. When introduced into human cells, point mutations in these interfaces impair the interactions between XPF-ERCC1 and SLX4 or SLX4IP, and disruption of the XPF-SLX4IP interface leads to cis-platin sensitivity. Furthermore, our data reveal the structure of the human XPF-ERCC1-SLX4IP-SLX4 complex with DNA bound at its active site, and they complete the structural characterisation of molecular interactions required to assemble the SMX complex.
External linksNat Commun / PubMed:41402316 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.8 Å
Structure data

53054

9qec

EMDB-53054, PDB-9qec:
Cryo-EM structure of the XPF-ERCC1-XPA complex
Method: EM (single particle) / Resolution: 2.9 Å

53055

9qed

EMDB-53055, PDB-9qed:
Cryo-EM structure of the XPF-ERCC1-SLX4(330-555)-SLX4IP complex
Method: EM (single particle) / Resolution: 3.2 Å

53058

9qee

EMDB-53058, PDB-9qee:
Cryo-EM structure of a DNA-bound XPF-ERCC1-SLX4(330-555)-SLX4IP complex
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-53059: Cryo-EM map of apo-XPF-ERCC1-SLX4(330-555)-SLX4IP from a DNA-containing sample.
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-53061: Cryo-EM map of the XPF-ERCC1-SLX4IP complex.
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-MN:
Unknown entry

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsHYDROLASE / DNA repair / endonuclease / multiprotein complex / DNA bound complex

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