Fig. 3: Mapping XPF–ERCC1 disease mutations and DNA repair pathway recruitment sites. | Nature Communications

Fig. 3: Mapping XPF–ERCC1 disease mutations and DNA repair pathway recruitment sites.

From: Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation

Fig. 3

a Top, a ribbon model of XPF–ERCC1 highlighting the spatially distinct binding sites of XPA and SLX4. XPA binds to the ERCC1 NLD (orange) and SLX4 binds to the XPF helical domain (green). The XPA peptide (residues 66–77) atoms are displayed as red spheres (PDB: 2JNW). The key SLX4 binding residue L230 sidechain atoms are also displayed as red spheres. Bottom, representative DNA structures targeted by XPF–ERCC1 through SLX4 (interstrand cross-link) or XPA (intrastrand cross-link) recruitment. b–d The molecular environment of patient-derived disease mutations are indicated on the structure, superposed with the cryo-EM map displayed close to the mutation site. Selected residues are displayed using stick rendering coloured by heteroatom. Residues associated with Fanconi anaemia (FA) patient mutations are coloured red whilst those associated with XP are coloured black. Black or orange dashed ellipses indicate the environment close to XP or FA mutations respectively. b Mutations in the XPF nuclease domain and ERCC1 NLD lie close to their interface and give rise to both FA and XP. c XP-associated mutations disrupt key structural contacts in the XPF RecA2 domain are shown overlaid with the composite cryo-EM map. d FA-associated mutations cluster within the XPF helical domain. The helical domain also contains the XP-associated mutant, I225 (black).

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